Calcium Homeostasis II Flashcards by Collin Huth

What is transcellular pathway of calcium absorption?

Calcium enters the apical membrane via calcium channels

Upon entering, calcium binds to calbindin-D9k

It is extruded across the basolateral membrane via a calcium ATPase - PMCA

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How does Vitamin D3 affect calcium reabsorption in the small intestine?

Increases absorption via the transcellular pathway

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How is phosphate absorbed in the intestine?

Paracellularly at tight junctions

Active transport involving a Na-phosphate cotransporter

Expression increased by Vitamin D3 and when dietary phosphate is low

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How does PTH affect calcium resabsoprtion in the kidney?

Stimulates TRPV5 activity in the PCT and TAL

Also stimulates reabsorption in the DCT

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How does PTH affect phosphate reabsorption in the kidney?

Increases urinary phosphate excretion by inhibiting reabsorption in the proximal and distal tubules

Promotes removal of sodium-dependent phosphate cotransporters from the luminal membrane

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What is the affect of PTH on 1a-renal hydroxylase?

Induces its synthesis in the PCT

Catalizes the formation of active vitamin D (1,25(OH)2D3)

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What is the active portion of PTH?

N-terminal region

Synthetic N-terminal fragments can induce all known actions of PTH

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How do chief cells regulate the quantity of intact PTH getting released?

Utilize intraglandular degradation of stored hormone

Secretory vesicles contain proteases that degrade intact PTH to inactive C-terminal fragments

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Describe the secretion of PTH in hypercalcemic and hypocalcemic states?

Hypercalcemic - decrease in secretion of intact PTH and an increase in release of inactive C-terminal fragments

Hypocalcemia - cheif cells release mostly intact PTH

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What is the principal physiological regulator of PTH secretion?

Plasma concentration of ionic calcium

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What is the response of chief cells to a decline in serum Ca?

Respond immediately to an acute decline in Ca by release preformed PTH

Decrease in intraglandular degradation of PTH, causing the release of more intact PTH

If prolonged, PTH gene transcription and an increased rate of chief cell proliferation occurs

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How do chief cells respond to hypercalcemia?

Intraglandular PTH breakdown increases

However, PTH secretion is not totally suppressed due to the basal rate of PTH secretion

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What is the calcium-sensing receptor (CaSR)?

G protein-coupled receptor that monitors minute-to-minute fluctuation in extracellular fluid Ca

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What is the effect of 1,25(OH)2D3 on PTH secretion?

Active Vitamin D3 inhibits PTH secretion

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What are the principal targets of PTH?

Kidneys and Bone

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What is the type 1 PTH receptor?

Binds both PTH and PTH releated protein (PTHrP)

Increases intracellular cAMP levels

What is the affect of PTH on bone?

Mobilizes calcium from bone by promoting the expression of RANK-L

Also downregulates the expression of OPG

What are the affects of PTH on the kidneys?

Increase Ca reabsorption by acting on Tubule cells

Promotes phosphate excretion

Induces 1a-renal hydroxylase expression

What is the direct effect of PTH excess?

Bone lesions due to PTH-induced bone resorption

What are the effects of PTH-induced hypercalcemia?

Fatigue

Vomiting, ab pain, constipation, pancreatitis

Neuro symptoms

Impaired kidney function due to kidney stones

Decreased membrane excitability

What are the clinical features of PTH deficiency?

Tetany from the spontaneous discharge of the peripheral nerves

What is Pseudohypoparathyroidism?

Rare familial disorder characterized by target tissue resistance to PTH

What is the function of PTH related protein?

Activates the same receptor as PTH

But is produced locally and acts as a paracrine or autocrine regulator

Regulates calcium flux through the placenta

What is humoral hypercalcemia of malignancy?

Syndrome associated with malignant tumors

PTHrP is the most common mediator of HHM

What is Vitamin D3 and D2?

D3 - lipid soluble vitamin formed by a photolytic reaction D2 - Formed from a platn sterol Both are inactive until modification by kidney or liver enzymes

How is Vitamin D activated?

First step: conversion of vitamin D to 25 hydroxyvitamin D, this step is essentially unregulated Second Step: Hydroxylation of 25(OH)D, this process is highly regulated and occurs in the PCTs of the kidneys

What is 25(OH)D?

Has very little activity Long circulatory half-life and the most abundant form in the blood This is what is measured when clincally assessing a patient's Vitamin D status

How is the activation of Vitamin D regulated?

Hypocalcemia and increased PTH have stimulatory affects on 1a-hydroxylase activity Increased calcium and low PTH decrease 1a-hydroxylase activity Active Vitamin D also has a negative feedback effect on the enzyme

What is Vitamin D binding protein?

Principal carrier of vitamin D and vitamin D metabolites

What are the principal targets of active Vitamin D?

Small intestine Bone Parathyroid glands

What is the affect of active Vitamin D on the small intestine?

Enhances calcium absorption by inducing expression of epithelial calcium channels and calbindin-D9k

What is the most apparent consequence of vitamin D deficiency?

Decreased bone mineralization

What is the effect of active vitamin D on the parathyroid glands?

Negative feedback effect on PTH secretion by inhibiting the expression of the PTH gene Induces the expression of the genes for the CaSR and the Vitamin D receptor

What is the effect of active vitmain D on bone?

Promotes mineralization by ensuring calcium and phosphate availability via its actions in the small intestine Promotes osteoclastogenesis by inducting RANK-L expression Suppresses OPG

What is the effect of active vitamin D on the kidney?

Modulates its own formation by inhibiting 1a-hydroxylase activity and stimulating 24-hydroxylase activity

What is the mechanism of action for Vitamin D?

Binds to Vitamin D receptor which acts as a ligand activated transcription factor Forms a heterodimer with an unliganded retinoid X receptor (RXR) The complex binds to a vitamin D response element in the regulatory region of a target gene

What results from vitamin D deficiency?

Rickets Osteomalacia

What is calcitonin?

Polypeptide hormone secreted by parafollicular cells in the thyroid Lowers plasma calcium levels by supressing bone resorption by osteoclasts

What stimulates the release of calcitonin?

High calcium levels Gi hormones, particularly gastrin