L5: Calcium Homeostasis Flashcards
__________ salts in bone provide structural integrity of the skeleton
Calcium phosphate salts in bone provide structural integrity of the skeleton
Sign of Hypocalcemia?
Involuntary muscle spasms - Tetany
Nerves and muscles overexcitable
Sign of Hypercalcemia?
Trousseau’s sign
Decreased Neuromuscular Sensitivity
Proportion of Free Calcium in the body?
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
Ca2+ and PO43-levels ____________ related so that [Ca2+] X [PO43-] is constant. If [Ca2+] X [PO43-] > __________, potential for spontaneous precipitation
Ca2+ and PO43-levels inversely related so that [Ca2+] X [PO43-] is constant. If [Ca2+] X [PO43-] > 40mg/dl, potential for spontaneous precipitation
Differentiated bone-forming cells which secrete bone matrix on which Ca and PO4 precipitate?
Osteoblasts -bone formation
Large multinucleated cell derived from monocytes whose function is to resorb (breakdown) bone
Osteoclasts -bone resorption
Mature bone cells (osteoblasts) enclosed in bone matrix?
Osteocytes -bone maintenance
3 Hormones that Regulate Calcium and Phosphate Levels?
- Parathyroid hormone (PTH)
- 1,25-dihydroxy Vitamin D3 (calcitriol)
- Calcitonin
________ is the dominant regulator of plasma free/ionised Ca2+. Its secretion is ________ related to Ca2+ concentration
PTH is the dominant regulator of plasma free/ionised Ca2+. Its secretion is inversely related to Ca2+ concentration
PTH Is released by ____________ in the parathyroid
Chief (Principal) cells
_________ binds to same receptor as PTH
Plays a minor role in Ca2+homeostasis
Secreted by many __________ => __________
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
Mechanisms of Ca2+ release from Bone?
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)
Effect of PTH on Plasma Ca2+ and PO4-?
What conditions can arise from mutations of CaSR?
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
Physiological Actions of PTH?
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-
Sources of Vitamind D?
Photodependent production in keratinocytes
Ingestion in the diet
Why is Vitamin D a true hormone but not a true vitamin?
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
Vitamin D plays an essential role in Ca2+ homeostasis by promoting ______________ and ______________________
Vitamin D plays an essential role in Ca2+ homeostasis by promoting intestinal Ca2+ absorption and renal reabsorption ( increases calbindin28K)
Enzyme key for Vitamin D synthesis
What increases its activity?
1a hydroxylase in the kidney
Regulation:
Increased by PTH
Increased by Hypophosphatemia
Where is Calcitonin Produced?
Produced in Thyroid C cells (Parafollicular Cells)
Increased Plasma Ca2+ levels => Increased Calcitonin Secretion
Physiological Role of Calcitonin?
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)
_______ is a functional antagonist of PTH
Calctitonin
Hyperfunctioning Parathyroid gland => Increased PTH
Casues/Clinical Presentation/Diagnosis?
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)
Hypofunctioning Parathyroid gland => Decreased PTH
Casues/Clinical Presentation/Diagnosis?
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*
G protein coupled receptor found on Chief (Principal) cells of Parathyroid?
Calcium Sensing Receptor (CaSR)
Low Extrasellar Calcium=> Increased PTH Secretion
Regulation of Calcium Reabsorption in Renal Epithelium?
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
Regulation of Calcium/Phosphate Reabsorption in the Gut?
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
True Versus Pseduo Hypoparathyroidism?
True: Decreased Ca2+ and Decreased PTH
Pseudo: Decreased Ca2+ and Increased PTH (PTH Resistiance)
