Calcium HORMONES Flashcards by Kyra Catedral

Parathyroid Hormone
s Secreted by the____ of the____

chief cells

parathyroid glands

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• Rapid response to reduced calcium (in minutes)

PTH

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PTH

Polypeptide:

Operates in tissues via cAMP
secondary messenger

84 amino acid residues

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Effects of PTH
Bone

First phase:_______
Second phase:______

osteolysis mediated by osteoblasts and osteocytes (calcium pump)

activation and formation of osteoclasts for bone resorption

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EFFECTS OF PTH

Kidney

Increased reabsorption of calcium in the thick ascending nephron loop and distal convoluted tubule

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EFFECTS of PTH

INTESTINE

Increased calcium absorption aided by 1, 25-dihydroxycholecalciferol (active metabolite of vitamin D)

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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)

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Monitors blood calcium levels

Adjusts PTH secretion

Found in PT gland

Calcium-Sensing Receptors

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secondary messengers

DIACYLGLYCEROL (DG)

INOSITOL TRISPHOSPHATE (IP3)

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PTH Lab Methods

Measurement of bio-intact PTH

PTH-related peptide

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Measurement of bio-intact PTH (using 2 antibodies that measure the____ and ____)

Amino terminus

caroboxylic acid terminus

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Measurement of bio-intact PTH (using 2 antibodies that measure the N-terminal and C-terminal)

ASSAY?

Two-site chemiluminescent assay

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PTH-related peptide
• produced by….

tumors (hypercalcemia of malignancy)

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• 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

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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

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Vitamin D…

is NOT a CLASSIC

is NOT a TRUE

is TRUE

NOT A CLASSIC HORMONE

NOT A TURE VITAMIN

A TRUE HORMONE

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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

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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