Calcium HORMONES Flashcards
Parathyroid Hormone
s Secreted by the____ of the____
chief cells
parathyroid glands
• Rapid response to reduced calcium (in minutes)
PTH
PTH
Polypeptide:
Operates in tissues via cAMP
secondary messenger
84 amino acid residues
Effects of PTH
Bone
First phase:_______
Second phase:______
osteolysis mediated by osteoblasts and osteocytes (calcium pump)
activation and formation of osteoclasts for bone resorption
EFFECTS OF PTH
Kidney
Increased reabsorption of calcium in the thick ascending nephron loop and distal convoluted tubule
EFFECTS of PTH
INTESTINE
Increased calcium absorption aided by 1, 25-dihydroxycholecalciferol (active metabolite of vitamin D)
Regulation of PTH
Calcium-Sensing Receptor
High plasma calcium level
• Activation of______
Increased levels of______ and _____ as secondary messengers
Release of calcium from intracellular stores
Decreased release of PTH
Phospholipase C
DIACYLGLYCEROL (DG) and
INOSITOL TRISPHOSPHATE (IP3)
Monitors blood calcium levels
Adjusts PTH secretion
Found in PT gland
Calcium-Sensing Receptors
secondary messengers
DIACYLGLYCEROL (DG)
INOSITOL TRISPHOSPHATE (IP3)
PTH Lab Methods
Measurement of bio-intact PTH
PTH-related peptide
Measurement of bio-intact PTH (using 2 antibodies that measure the____ and ____)
Amino terminus
caroboxylic acid terminus
Measurement of bio-intact PTH (using 2 antibodies that measure the N-terminal and C-terminal)
ASSAY?
Two-site chemiluminescent assay
PTH-related peptide
• produced by….
tumors (hypercalcemia of malignancy)
• 141 AA (shares the same homology with PTH in the first 13 AA and can activate PTH receptor)
• its normal physiological role is not clear
PTH-related peptide
PTH related peptide
•____AA (shares the same homology with PTH in the first____ AA and can activate PTH receptor)
• its normal physiological role is not clear
141 AA
13 AA
Vitamin D…
is NOT a CLASSIC
is NOT a TRUE
is TRUE
NOT A CLASSIC HORMONE
NOT A TURE VITAMIN
A TRUE HORMONE
WHY???
• NOT A CLASSIC HORMONE:
• NOT A TRUE VITAMIN:
• A TRUE HORMONE:
it is not produced and secreted by an endocrine “gland”.
it can be synthesized de novo
it can act on distant target cells to evoke responses after binding to high affinity receptors
Vitamin D
______-soluble hormone
• binds to a typical intracellular receptor
CARRIER PROTEIN:______
Lipid
hydroxylated a-globulin
Sources of Vitamin D
Skin Synthesis:
When exposed to UVB light,_________ in the skin is converted to______
Dietary Intake:
Cholecalciferol (Vitamin D3) is obtained from_______
Ergocalciferol (Vitamin D2) is obtained from______
7-dehydrocholesterol; cholecalciferol (Vitamin D3)
animal sources, like fatty fish and fortified foods
plant sources and supplements.
What converts 7-dehydrocholesterol to Cholecalciferol (Vitamin D3)
Ultraviolet light
Transport to the Liver
Cholecalciferol (Vitamin D3) and ergocalciferol (Vitamin D2) are transported to the____ via the bloodstream, bound to the Vitamin D-binding protein (DBP).
liver
Liver Hydroxylation (First Activation Step)
In the liver, Vitamin D3/D2 undergoes hydroxylation by the enzyme______ to form________.
25-hydroxylase; calcidiol (25-hydroxyvitamin D)
• This is the main circulating form of Vitamin D in the blood.
• It is inactive but serves as a marker for Vitamin D status due to its long half-life.
Calcidiol
Transport to the Kidneys
Calcidiol (25-hydroxyvitamin D) is transported to the kidneys for further activation.
This transport still relies on the Vitamin D-binding protein (DBP).
Kidney Hydroxylation (Second Activation Step)
In the kidneys, calcidiol (25-OH Vitamin D) is converted to the active form,_______ by the enzyme _______
calcitriol (1,25-dihydroxyvitamin D)
1-α-hydroxylase
Regulation of 1-α-hydroxylase:
What stimulates the activity of 1-α-hydroxylase during low calcium levels?
• Calcium and Phosphate Levels: High levels inhibit the enzyme to prevent excessive production of calcitriol.
Parathyroid Hormone (PTH)
Biological Actions of Calcitriol (Active Vitamin D)
Intestinal Absorption of Calcium:
• Calcitriol increases the production of calcium-binding proteins (e.g., calbindin) in intestinal cells, enhancing calcium absorption from food.
Bone Resorption:
• Calcitriol works with PTH to mobilize calcium and phosphate from bone during times of deficiency.
Renal Reabsorption:
• It reduces calcium and phosphate excretion in the kidneys, maintaining blood levels.
Inactivation Pathway
Excess calcidiol (25-OH Vitamin D) and calcitriol (1,25-dihydroxyvitamin D) are converted to inactive metabolites by the enzyme______
Inactive Metabolites:
• Examples______, which is excreted to prevent toxicity
24-hydroxylase
include 24,25-dihydroxyvitamin D
: Converts Vitamin D into calcidiol (25-OH Vitamin D).
: Converts calcidiol into the active form, calcitriol (1,25(OH)₂D).
: Converts excess calcitriol or calcidiol into inactive forms.
25-Hydroxylase (Liver)
1-α-Hydroxylase (Kidneys)
24-Hydroxylase (Kidneys)
Vitamin D3 Lab Methods
Better marker:
• half life???
25-HYDROXY VITAMIN D (longer half-
life)
2-3 weeks versus 5-8 hours
Vitamin D3 Lab Methods
Reference method:
Values are influenced by_____
DUAL MASS SPECTROMETRY
sunlight exposure
Calcitonin
Acts to decrease plasma______
PTH and Vitamin D3 regulation dominate (more powerful secretion than calcitonin).
Secreted by the _______of the thyroid gland
Target cell:_____
Calcium levels
parafollicular cells or C cells
osteoclast
Major effect of calcitonin
• rapid fall in Ca + caused by inhibition of bone resorption
LABORATORY METHODS: CALCITONIN
Serum Calcitonin
Pentagastrin (Pg) Stimulation Test
Calcium Stimulation Test
• As tumor marker for detecting residual thyroid tissue or metastasis in patients with Medullary Thyroid Carcinoma (MTC)
• It should be measured_______
Serum Calcitonin
before and 6 months after surgery
• IV administration (0.5 ug / kg body weight) over 5 seconds
• Blood samples: baseline, 1, 2, 5, and 10 minutes after the start of infusion
Pentagastrin (Pg) Stimulation Test
Pentagastrin (Pg) Stimulation Test
• IV administration (________) over 5 seconds
• Blood samples: baseline,________ after the start of infusion
0.5 ug / kg body weight
1, 2, 5, and 10 minutes
• IV administration of calcium gluconate (2.5 mg/ kg body weight) over 30-60 seconds
• Blood samples: baseline, 1, 2, and 5 minutes after the start of infusion
• Less sensitive than Pg Test, but if combined with Pg Test, it enhances the sensitivity of the Pg Test to diagnose medullary thyroid carcinoma
Calcium Stimulation Test
Calcium Stimulation Test
• IV administration of______(_____) over 30-60 seconds
• Blood samples: baseline, _____minutes after the start of infusion
• Less sensitive than Pg Test, but if combined with Pg Test, it enhances the sensitivity of the Pg Test to diagnose medullary thyroid carcinoma
calcium gluconate ; 2.5 mg
/ kg body weight
1, 2, and 5
calcium stimulation test
of plasma calcitonin = C Cell Hyperplasia
> 100 ng/L
Pg test
Normal (80% of adults)
<10 ng/L
Pg test
5% of normal adults
> 30 but <50 ng/ L
Pg test
Possible MTC or other thyroid pathology
> 50 but <100 ng/L
Pg test
Probable MTC
> 100 ng/L
Pg test
Basal or post-Pg CT value____
C cell pathology or residual tissue in MEN 2 patients and MTC patients after surgery
> 10 pg/mL
