Calcium Regulation and Function in Biology

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Questions and Answers

What is the primary function of parathyroid hormone (PTH)?

Increase blood calcium levels (correct)

Promote bone formation

Decrease blood calcium levels

Enhance muscle contraction

Which of the following is NOT a role of calcium (Ca2+) in the body?

Hormone production (correct)

Blood clotting

Muscle contraction

Neurotransmitter release

How does an increase in cytosolic calcium concentration primarily affect muscle cells?

Inhibits neurotransmitter release

Increases the rate of muscle relaxation

Initiates muscle contraction (correct)

Decreases intracellular signaling

What role does calmodulin play in calcium signaling?

It is a calcium-sensing protein Signup and view all the answers

Which of the following mechanisms is responsible for maintaining low cytosolic calcium levels?

Calcium exchangers and pumps Signup and view all the answers

What is the main storage site for intracellular calcium in muscle cells?

Sarcoplasmic reticulum Signup and view all the answers

What is a consequence of calcium overload inside cells?

Neurodegenerative processes Signup and view all the answers

Which condition is associated with hypercalcaemia?

Cardiac arrhythmia Signup and view all the answers

What is the normal range of extracellular calcium concentration?

2.2 - 2.55 mM Signup and view all the answers

What unique function do osteocytes serve in bone metabolism?

Maintaining metabolism and nutrient exchange Signup and view all the answers

What substance do osteoclasts release to aid in bone resorption?

H+ ions Signup and view all the answers

Hypocalcaemia may lead to which of the following conditions?

Tetany Signup and view all the answers

Which of the following forms of calcium is not found in the bloodstream?

Mineralized calcium Signup and view all the answers

What is the primary role of osteoblasts in bone formation?

Mineralizing bone matrix Signup and view all the answers

What is the active form of vitamin D3 in the body?

Calcitriol Signup and view all the answers

Which of the following statements about calcitonin is correct?

It is synthesized by the thyroid's parafollicular cells. Signup and view all the answers

What primary function does the active form of vitamin D3 serve related to calcium?

Stimulates intestinal calcium uptake. Signup and view all the answers

Which hormone acts as a physiological antagonist to PTH?

Calcitonin Signup and view all the answers

What is a common cause of hypocalcaemia?

Deficiency of vitamin D3 Signup and view all the answers

Why is calcitonin clinically used in the treatment of hypercalcaemia?

It reduces osteoclastic resorption. Signup and view all the answers

What condition results from reduced or absent synthesis of PTH?

Hypoparathyroidism Signup and view all the answers

Which of the following hormones is synthesized by chief cells in the parathyroid glands?

Parathyroid hormone (PTH) Signup and view all the answers

What factor is the dominant regulator of PTH secretion?

Plasma Ca2+ levels Signup and view all the answers

Which of the following is a treatment for hypoparathyroidism?

Calcium and Vitamin D Signup and view all the answers

What is the role of osteoclasts in the presence of PTH?

Increase bone resorption Signup and view all the answers

Which of these best describes hypoparathyroidism caused by a congenital defect in PTH GPCR signaling?

PTH-ineffective hypoparathyroidism Signup and view all the answers

What happens to plasma phosphate levels when PTH is active?

They decrease Signup and view all the answers

What is the effect of Vitamin D on PTH secretion?

Reduces PTH secretion Signup and view all the answers

Which of the following options does not describe a type of hypoparathyroidism?

Primary hyperparathyroidism Signup and view all the answers

Study Notes

Calcium Regulation & the Parathyroid

Calcium is a vital ion, both intracellularly and extracellularly
A major component of bone (~50% bone weight), primarily as hydroxyapatite.
99% of calcium in bone and teeth.
Cystolic calcium levels at rest are significantly lower than extracellular levels (~12,000-fold lower).
Calcium levels are regulated through pumps, ion channels, and exchangers.
Calcium plays a crucial role in neurons for synaptic transmission, initiating neurotransmitter release.
Calcium is an intracellular messenger, impacting processes like muscle contraction.

Calcium as a Second Messenger

Calcium is essential for cardiac muscle contraction—a discovery by Ringer in 1883
Intracellular calcium triggers muscle contractions (Heilbrunn, 1940s)
Calcium activates contractile proteins (e.g. troponin-C, actin) and regulates intracellular calcium levels via the sarcoplasmic reticulum (Ebashi, 1960s).
Calmodulin is a ubiquitous calcium-sensing protein (discovered in 1973).

Calcium as a Signaling Molecule

Calcium acts as a signaling molecule, influencing cellular activities like altering enzyme activity, exocytosis, and movement.

Cytosolic Calcium Changes in Signaling

Significant increases in cytosolic calcium (up to 20-fold) occur in response to various stimuli.
Fast signals trigger muscle contractions
Sustained signals stimulate transmitter secretion
Long-term changes affect gene expression

Intracellular Calcium Storage

Intracellular calcium is primarily stored within the endoplasmic reticulum (ER) or the sarcoplasmic reticulum (SR) in muscle cells
Calcium signaling is compartmentalised
Calcium signaling exhibits variations in amplitude, frequency, and shape, including calcium sparks and puffs."

Calcium and Blood Clotting

Calcium is necessary for blood clotting.
Clotting factors X, VII, IX, and protein C contain calcium-binding domains

Calcium Signaling in Disease

Calcium overload inside cells is toxic.
This can cause muscle dysfunction (e.g., heart failure) and neurodegenerative processes (e.g., diabetic neuropathies, Alzheimer's disease).
Disruption in ER calcium homeostasis contributes to beta-amyloid synthesis.
High plasma calcium (hypercalcemia) can lead to cardiac arrhythmias and reduced neuromuscular transmission
Low plasma calcium (hypocalcemia) causes tetany, epilepsy, and blood clotting problems

Extracellular Calcium Regulation

Extracellular calcium (Ca2+) levels are carefully controlled by the body.
Normal levels range from 2.2 to 2.55 mM

Calcium Fluxes in the Normal Adult

Calcium is absorbed from the small intestine and is regulated based on various factors like PTH, calcitriol, and calcitonin
Calcium moves actively through electrochemical gradients to maintain the delicate balance between bone, extracellular fluid (ECF), and kidneys

Bone Growth and Metabolism

Bone growth and calcium metabolism are intertwined processes.
Epiphyses are the ends of long bones.
Diaphysis is the shaft of long bones and epiphyseal plates are crucial for bone growth.
Bone growth occurs by dividing chondrocytes, which add length and are then replaced by bone tissue as it develops.

Bone Cells

Osteoblasts are bone-forming cells that secrete osteoid (forming bone matrix) which is then mineralized
Osteocytes mature from osteoblasts, no longer producing matrix but contributing to metabolism.
Osteoclasts are responsible for resorbing and degrading existing bone, contributing to calcium regulation and bone remodeling, essentially the opposite of osteoblasts.

Osteoclasts

Osteoclasts release hydrogen ions into the bone matrix to acidify the area.
This acidification process weakens the mineral content of the bone matrix, causing the release of calcium ions.
Hydrolytic enzymes (e.g., cathepsins) are released, dissolving the bone's organic components.

Osteoporosis

Osteoporosis is a disease of bone growth and metabolism, where bone resorption exceeds deposition
Potential factors are inadequate calcium intake, genetics, hormones, and smoking.
Treatment often includes bisphosphonates which inhibit the activation of enzymes using pyrophosphate.

Soluble Factors Affecting Calcium Availability

Hormones, as soluble factors, can influence the availability of calcium in the body.

Parathyroid Glands

Four parathyroid glands are present, situated posteriorly to the thyroid gland, embedded within its lobes.
Each is approximately 40-60mg in weight
Variations exist in the number, size, and location of the parathyroid glands

Parathyroid Hormone (PTH)

PTH is synthesized as a preprohormone by the parathyroid chief cells.
The active form of PTH (84 amino acids) is cleaved from the preprohormone before its release.
PTH release is triggered by low blood calcium levels; therefore is part of a negative feedback system, and high calcium inhibits release.
PTH is released by exocytosis and is continuously synthesized though the body degrades it if not released.
Vitamin D regulates PTH as a secondary mechanism.

PTH's Biological Activity

PTH increases plasma calcium levels by decreasing plasma phosphate levels.
PTH directly stimulates osteoclasts which release calcium and phosphate into the bloodstream, increasing bone resorption
PTH causes an increase in calcium reabsorption and phosphate excretion in the kidney.
PTH stimulates vitamin D3 synthesis, promoting calcium reabsorption in the intestine.

Calcium Regulation by PTH Secretion

Calcium is the dominant regulator of PTH secretion.
Continuous secretion of PTH.
Maximum PTH secretion occurs at plasma Ca < 3.5 mg/dL.
Parathyroid gland chief cells have specialized calcium receptors.
Changes in extracellular fluid calcium trigger PTH release (seconds).

Hyperparathyroidism

Hyperparathyroidism results from excessive PTH secretion due to benign tumors or hyperplasia of the parathyroid glands
Hypercalcemia results from heightened bone resorption, intestinal calcium absorption, and renal tubular reabsorption
This excessive PTH secretion leads to calcium homeostatic loss.
The pathophysiology involves both PTH excess and concurrent increase in 1,25-(OH)2D, commonly from a solitary parathyroid adenoma
Treatment usually entails hydration, intravenous bisphosphonates, or calcitonin for moderate cases; treating the underlying cause of the disorder in severe cases is advised.

Primary Hyperparathyroidism

One of the most common endocrine disorders; often impacting women more than men (ratio 4:1).
Typically sporadic, featuring a solitary parathyroid adenoma as a trigger.
PTH increases blood Ca levels, causing bone damage via demineralization which causes bone cysts, and phalangeal erosion
Surgical excision of the adenoma is often curative (>90% successful rate).

Hypoparathyroidism

Hypoparathyroidism is a far less common condition than hyperparathyroidism.
The causes include PTH deficiency (reduced or absent PTH synthesis). This could be due to inadvertent parathyroid tissue removal during surgery or synthesis of biologically inactive PTH.
PTH resistance (pseudohypoparathyroidism) which results when there is a lack of proper response to given PTH or abnormalities in signalling.
This often results from a congenital defect in PTH GPCR signalling.
Treatment entails calcium and vitamin D supplementation.

Other Calcium-Regulating Hormones

The primary calcium regulating hormones are PTH and Calcitonin.

Vitamin D

Vitamin D is crucial for calcium homeostasis.
It is obtained from sun exposure, diet, and supplements.
Vitamin D synthesized in the skin is a precursor and requires hydroxylation reactions in the liver and kidneys (often stimulated by PTH) to be converted to calcitriol (1,25-dihydroxycholecalciferol), its biologically active form
It is carried by vitamin D-binding protein (VDBP) to target cells
It regulates genes for intestinal calcium uptake, bone mineralization, kidney phosphate uptake, thyroid & parathyroid function and immune function.
Vitamin D deficiency is a frequent cause of hypocalcemia

Vitamin D Synthesis

Vitamin D is synthesized from cholesterol via UV exposure or intake of foods rich in vitamin D or dietary supplements
The precursor requires two sequential hydroxylation reactions to become active
The first hydroxylation converts the vitamin into 25(OH)D, in the liver, followed by the second hydroxylation, in the kidneys to 1,25-(OH)2D.
The second hydroxylation reaction is stimulated by parathyroid hormone.
Active Vitamin D (calcitriol) promotes calcium absorption in the intestines and bone mineralization.

Vitamin D3

Vitamin D3 is carried by vitamin D-binding protein (VDBP) and binds to nuclear receptors
Regulates genes for important body functions like intestinal calcium uptake, bone mineralization, kidney phosphate uptake, and thyroid & parathyroid function, immune function and reduced inflammation

Calcitonin

Calcitonin is secreted from C-cells in the thyroid gland
Calcitonin acts to decrease plasma calcium levels, providing a physiological antagonist to PTH
Calcitonin's role in normal calcium regulation is significant, but it may play a more crucial role in regulating bone remodeling
Clinically, calcitonin is used to treat certain conditions like hypercalcemia and Paget's disease

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Description

Explore the critical roles of calcium in the human body, including its regulation through various cellular mechanisms and its function as a second messenger in muscle contraction. This quiz covers aspects of intracellular and extracellular calcium, neurotransmitter release, and cardiac muscle functionality. Test your understanding of calcium's biological significance and its involvement in cellular processes.