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SEM3: PATH30210 Endocrine Health/Disease > L5: Calcium Homeostasis > Flashcards

L5: Calcium Homeostasis Flashcards

1
Q

__________ salts in bone provide structural integrity of the skeleton

A

Calcium phosphate salts in bone provide structural integrity of the skeleton

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2
Q

Sign of Hypocalcemia?

A

Involuntary muscle spasms - Tetany

Nerves and muscles overexcitable

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3
Q

Sign of Hypercalcemia?

A

Trousseau’s sign

Decreased Neuromuscular Sensitivity

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4
Q

Proportion of Free Calcium in the body?

A

99% Calcium in bones is NOT accessible

.9% intracellular

.1% extracellular (VERY IMPORTANT) -free fraction tightly regulated, with daily variation < 10%

  • 50% bound (proteins, CaPO4, Cacitrate)
  • 50% free (ionised) Ca2+ biologically active
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5
Q

Ca2+ and PO43-levels ____________ related so that [Ca2+] X [PO43-] is constant. If [Ca2+] X [PO43-] > __________, potential for spontaneous precipitation

A

Ca2+ and PO43-levels inversely related so that [Ca2+] X [PO43-] is constant. If [Ca2+] X [PO43-] > 40mg/dl, potential for spontaneous precipitation

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6
Q

Differentiated bone-forming cells which secrete bone matrix on which Ca and PO4 precipitate?

A

Osteoblasts -bone formation

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7
Q

Large multinucleated cell derived from monocytes whose function is to resorb (breakdown) bone

A

Osteoclasts -bone resorption

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8
Q

Mature bone cells (osteoblasts) enclosed in bone matrix?

A

Osteocytes -bone maintenance

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9
Q

3 Hormones that Regulate Calcium and Phosphate Levels?

A
  1. Parathyroid hormone (PTH)
  2. 1,25-dihydroxy Vitamin D3 (calcitriol)
  3. Calcitonin
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10
Q

________ is the dominant regulator of plasma free/ionised Ca2+. Its secretion is ________ related to Ca2+ concentration

A

PTH is the dominant regulator of plasma free/ionised Ca2+. Its secretion is inversely related to Ca2+ concentration

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11
Q

PTH Is released by ____________ in the parathyroid

A

Chief (Principal) cells

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12
Q

_________ binds to same receptor as PTH
Plays a minor role in Ca2+homeostasis
Secreted by many __________ => __________

A

PTH related peptide protein (PTHrP) binds to same receptor as PTH
Plays a minor role in Ca2+homeostasis
Secreted by many tumours => hypercalcemia of malignancy

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13
Q

Mechanisms of Ca2+ release from Bone?

A

Osteocytic Osteolysis (Rapid, Minutes): non-mineralized calcium exchanged with plasma. Doesn’t decrease bone mass, activation of Ca pumps pumping calcium out from cauliculi into plasma

Osteocytic Reabsorption (Slow, Weeks-Months)

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14
Q

Effect of PTH on Plasma Ca2+ and PO4-?

A
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15
Q

What conditions can arise from mutations of CaSR?

A

Activating Mutations: Mimics effect of calcium binding => No PTH Excretion => Familial Hypoparathyroidism w/ Hypercalciuria

Inactivating Mutations: Receptor no longer able to sense calcium => Excessive PTH released => Excessive Calcium levels

  • Familial Benign Hypocalciuric Hypercalcemia (FHH)
  • Neonatal Severe Primary Pyperparathyroidism
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16
Q

Physiological Actions of PTH?

A

PTH acts DIRECTLY on bone: INCREASED Ca2+release

PTH acts DIRECTLY on kidney (distal tubule):

  • INCREASED Ca2+reabsorption
  • DECREASED PO43- reabsorption => urinary excretion

PTH acts INDIRECTLY on intestine:: Stimulates Vitamin D3 synthesis in kidney => D3 Promotes absorption of calcium in intestines

Overall action of PTH is to prevent/reverse hypocalcemia: Increases Ca2 and decreasing PO43-

17
Q

Sources of Vitamind D?

A

Photodependent production in keratinocytes
Ingestion in the diet

18
Q

Why is Vitamin D a true hormone but not a true vitamin?

A

Not a true “vitamin” since it can be synthesized de novo

Vitamin D is a ‘true’ hormone since it has an endocrine mode of action, acting on distant target tissues via binding to high-affinity receptors

19
Q

Vitamin D plays an essential role in Ca2+ homeostasis by promoting ______________ and ______________________

A

Vitamin D plays an essential role in Ca2+ homeostasis by promoting intestinal Ca2+ absorption and renal reabsorption ( increases calbindin28K)

20
Q

Enzyme key for Vitamin D synthesis

What increases its activity?

A

1a hydroxylase in the kidney

Regulation:
Increased by PTH
Increased by Hypophosphatemia

21
Q

Where is Calcitonin Produced?

A

Produced in Thyroid C cells (Parafollicular Cells)

Increased Plasma Ca2+ levels => Increased Calcitonin Secretion

22
Q

Physiological Role of Calcitonin?

A

Major physiological actions:

  • inhibits osteoclastic activity in bone
  • inhibits Ca2+reabsorption by kidney
  • inhibits Ca2+ absorption by the intestine

Acts as a functional antagonist of PTH (decreases plasma Ca2+ levels)

23
Q

_______ is a functional antagonist of PTH

A

Calctitonin

24
Q

Hyperfunctioning Parathyroid gland => Increased PTH

Casues/Clinical Presentation/Diagnosis?

A

Primary Hyperparathyroidism

Casues

  • 85% of cases due to single parathyroid adenoma
  • 15% of cases due to hyperplasia

Clinical Presentation

  • Asymtomatic w/ elevated calcium on routine labs
  • Bones unexpected fracture/osteopenia/osteoporosis
  • Stones
  • Moans
  • Groans

Diagnosis:

  • elevated calcium and PTH
  • alkaline phosphatase (Bone Turnover)
25
Q

Hypofunctioning Parathyroid gland => Decreased PTH

Casues/Clinical Presentation/Diagnosis?

A

Primary Hypoparathyroidism

Cause

  • trauma during thyroidectomy
  • congenital deficiency (DiGeorge syndrome)

Clinical Presentation

  • psychological disturbances (mood swings, anxiety, hyperirritability)
  • wheezing and dyspnea (due to tetany)
  • spasms of the hands and feet, muscle cramps)

Diagnosis

  • low or absent PTH
  • hypocalcemia*
26
Q

G protein coupled receptor found on Chief (Principal) cells of Parathyroid?

A

Calcium Sensing Receptor (CaSR)

Low Extrasellar Calcium=> Increased PTH Secretion

27
Q

Regulation of Calcium Reabsorption in Renal Epithelium?

A

Calbindin28k upregulated by PTH Chelates free calcium => favorable gradient for continued absorption from urine

Apical Ca2+channel upregulated by PTH => Number of channls in apical side of cells increased => Increased calcium absorption

28
Q

Regulation of Calcium/Phosphate Reabsorption in the Gut?

A

Calcium Absorption in the Gut upregulated by 1,25-dihydroxy Vitamin D3 (Calcitriol):

  • INCREASED PHOSPHATE ABSORPTION
  • Upregulates Calbindin -D chelates free calcium => INCREASED CALCIUM ABSORPTION
29
Q

True Versus Pseduo Hypoparathyroidism?

A

True: Decreased Ca2+ and Decreased PTH

Pseudo: Decreased Ca2+ and Increased PTH (PTH Resistiance)

SEM3: PATH30210 Endocrine Health/Disease (25 decks)

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