5 Ca/PO4 Regulation Flashcards

1
Q

Why are calcium levels so tightly regulated?

A

Calcium is fundamentally important to ALL biologic systems

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2
Q

What is a normal level of blood calcium?

A

Total (free and bound) 8.6 to 10.6mg/dL with daily variation < 10%

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3
Q

How much of plasma calcium is bound?

A

50%

The unbound, ionized form is active (so about 5 mg/dL with daily variation <2%)

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4
Q

99% of Ca2+ is in …

A

Crystalline form found in teeth and bone (1 and 2 kg)

Of the 1%, remaining, 0.9% is contained in soft tissues and 0.1% is in the ECF (1/2 of that is free and diffusable)

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5
Q

What is the normal daily intake of calcium from diet?

A

1000mg

Of that, 800mg is excreted in feces and 200mg excreted in urine

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6
Q

What is the normal distribution of phosphate in the body?

A

85% in bone and teeth, 15% in muscle

In cells, >80% in mitochondria and remaining in cytosol

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7
Q

What is the normal dietary intake of phosphate?

A

1000mg

350mg excreted in feces, 650mg excreted in urine

If there’s a demand for phosphate, the kidney can reabsorbed a lot

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8
Q

Calcium and phosphate levels in the blood stream are regulated by..

A

Parathyroid hormone (PTH) and vitamin D

Involves the interaction of bone, intestine, and kidney (target organs for PTH)

PTH is released in response to a drop in blood calcium —> acts to normalize Ca by acting on these organs

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9
Q

Parathyroid glands release PTH from _________

A

Chief cells

Released in response to hypocalcemia (low blood Ca2+)

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10
Q

Effect of PTH on bone

A

Activates osteoclasts —> calcium and phosphate ions released to blood

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11
Q

Effect of PTH on Intestines

A

Increases calcium absorption from food

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12
Q

Effect of PTH on Kidneys

A

Promotes activation of Vitamin D (which increases calcium absorption from food)

Increases calcium reabsorption and phosphate secretion in kidney

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13
Q

What are the two pools of calcium in bone?

A

Stable pool - consists of mature mineralized bone, composed primarily of hydroxyapatite; undergoes resorption by SLOW breakdown of crystals to liberate Ca and PO4

Labile pool - consists of bone fluid, composed primarily of amorphous crystals; undergoes osteopathic osteolysis for FAST release of Ca and PO4

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14
Q

Which calcium pool in the bone is used for minute to minute adjustments to Calcium/phosphate levels?

A

Labile pool (can undergo osteolytic osteolysis)

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15
Q

What separates the bone itself from the plasma in the osteon canals?

A

Osteocytic-osteoblastic bone membrane

This is where fast exchange from labile pool occurs

Has large surface area —> large influx between bone fluid and plasma

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16
Q

In fast exchange from the labile pool, Ca2+ is moved into the plasma by means of …

A

PTH-activated Ca2+ pumps located in the osteocytic-osteoblastic membrane

17
Q

In slow exchange, Ca2+ is moved from the stable pool into the plasma by means of …

A

PTH-induced dissolution of the bone

18
Q

PTH exerts what two direct effects in the kidney

A

Stimulates Ca reabsorption

Inhibits PO4 reabsorption

—> Phosphaturic effect (eliminates PO4 and leads to increase in urine cAMP)

19
Q

What does measuring urine cAMP tell us?

A

Gives you an index of PTH status. Increased PTH secretion leads to PO4 secretion (because you don’t want CaPO4 crystals) which in turn leads to an increase in urine cAMP

20
Q

How does PTH effect vitamin D

A

Activates vitamin D by stimulating 1-alpha hydroxylase activity in kidney, which converts the inactive precursor into the active form.

Activated vitamin D targets the intestine, bone, and kidney to collectively regulate CALBINDIN synthesis, and Ca2+ and PO43- levels in the plasma

21
Q

Steps in the “life cycle” of vitamin D

A
  1. Vitamin D is inactive when it enters the blood from skin or diet
  2. Addition of an (OH) group on carbon 25 in the liver (via 25-hydroxylase)
  3. Addition of an (OH) group on carbon 1 in the kidney (via 1a-hydroxylase) —> 1,25 dihydroxycholecalciferol (active form)
  4. Addition of an (OH) group on carbon 24 produces INACTIVE 24,25-dihydroxycholecalciferol
22
Q

Actions of Vitamin D on bone

A

Synergizes with PTH to stimulate resorption and remodeling and to mobilize Ca and PO4

23
Q

Actions of vitamin D on the kidney

A

Promotes calcium reabsorption from distal tubule and proximal tubular reabsorption of phosphate

24
Q

Actions of vitamin D on small intestine

A

Increases Ca absorption by increasing expression of calbindin

Calcium diffuses into cell, binds to calbindin, and is pumped across the basolateral membrane by Ca-ATPase

25
Q

What is a common symptom of chronic vitamin D intake?

A

Confusion

Due to excess serum Ca2+

26
Q

What does calcitonin do?

A

“Tones down” calcium levels

Stimulus of calcitonin release is an increased plasma calcium level

Calcitonin decreases plasma Ca and PO4 by inhibiting bone resorption and tubular reabsorption (BONES AND KIDNEYS ONLY, no effect on intestine)

Except for the intestine, it’s basically the opposite of PTH

27
Q

Where does calcitonin come from?

A

Secreted by parafollicular cells of the thyroid gland

28
Q

Why is calcitonin important?

A

May prevent post-prandial hypercalcemia

Deficiency does not lead to dramatic hypercalcemia though 🤷‍♀️

Excess (C cell tumors) calcitonin DOES NOT produce hypocalcemia

MAY be protective against excessive bone resorption or when demand for Ca increases (pregnancy, lactation, growth)

29
Q

Primary hyperparathyroidism is most commonly caused by…

A

PTH-secreting adenoma, resulting in elevated PTH levels in the plasma

30
Q

What are the clinical consequences of primary hyperparathyroidism?

A

Plasma: hypercalcemia and hypophosphatemia
Urine: increased levels of phosphate, cAMP and hypercalciuria

“Stones, bones, and groans”
• Osteoporosis, osteomalacia
• Kidney stones (Ca-PO4 or Ca-oxalate)
• Muscle weakness and decreased muscle excitability (b/c increased calcium interferes with Na+ channels)

31
Q

Hypoparathyroidism is usually caused by…

A

Inadvertent consequences of thyroid surgery for treatment of cancer or Graves’ disease

AKA surgical hypoparathyroidism

32
Q

Characteristics of hypoparathyroidism

A

Low PTH levels, hypocalcemia, hyperphosphatemia

Complications:
Hypocalcemia may induce tetany
Hyperreflexia, spontaneous twitching, muscle cramps
Convulsions

33
Q

What is a positive Trousseau’s sign

A

Forearm spasm with BP cuff inflation

Indicates hypoparathyroidism

34
Q

What is humoral hypercalcemia of malignancy?

A

Malignant cell clusters (breast, lung) that secrete PTH-related peptide (PTH-rp) and bind to the PTH receptor

PTH-rp has all the actions of PTH (increased bone resorption, increased renal calcium reabsorption and inhibition of renal phosphate reabsorption —> hypercalcemia and hypophosphatemia) but PTH levels are LOW

No intestinal effect though

35
Q

Insufficient vitamin D, Ca and PO4 to mineralized growing bone —> growth failure and skeletal anomalies

A

Rickets (def of vitamin D in childhood)

SSx:
Hypocalcemia, elevated PTH levels
Tetany, muscle weakness, fractures

Common in developing countries: inadequate vitamin D, calcium, diet and/or sunlight exposure

36
Q

Deficiency of vitamin D in adulthood leads to …

A

Osteomalacia

Usually from dietary deficiency or intestinal surgery, or malabsorption syndrome (ie celiac)

SSx:
Softened, weakened bones, frequent fractures
Hypocalcemic tetany, hypocalcemia

37
Q

Autosomal dominant disorder associated with a defective Gs in kidney bone —> defective signal transduction

A

Pseudohyperparathyroidism or Albright’s hereditary osteodystrophy

Will have elevated PTH levels, hypocalcemia, hyperphosphatemia

SSx:
Short stature
Short neck
Obesity
Shortened 4th metatarsals and metacarpals