Calcium

Question 1

What are the key chemical characteristics of calcium?

Answer 1

-Calcium is found primarily as Ca2+
-It is water-soluble but moves slowly across compartments due to membrane permeability.
-Intracellular Ca²⁺ concentration is very low and tightly regulated by pumps.
-acts as a messenger, initiating processes rather than directly causing functions.

Question 2

How does calcium function as a messenger in cells? what allows it to initiate functions?

Answer 2

A rapid rise and fall in cytoplasmic calcium drives processes like:

-Nerve conduction.
-Muscle contraction.
-Enzyme regulation (via proteins like calmodulin).

Calcium interacts with voltage-gated channels and binding proteins to propagate signals.

Question 3

What are the biological functions of calcium in the body?

Answer 3

1) bone mineralization
- 99% of Ca in bone
2) blood clotting
3) nerve/muscle contraction
4) signal transduction

Question 4

explain how an indirect influx of Ca++ impacts membrane function?

Answer 4

Ca++ changes electrical properties of a cell through ligand-gated channels

Question 5

explain how a direct influx of Ca impacts membrane function?

Answer 5

a change in cytosolic Ca levels through ligand gated channels causes it to act as a second messenger

Question 6

what is calmodulin? what is its interaction with Ca2+? what does this stimulate?

Answer 6

calmodulin is a calcium-binding protein that acts as an intracellular receptor for Ca2+

1) Ca2+ influx into the cell causes binding to calmodulin
2) binding causes conformational change
3) calcium-calmodulin complex interacts with enzymes, causing cellular functions to occur such as:

-phosphorylase kinase
-myosin kinase (muscle contraction)
-calmodulin protien kinase (memory/learning)

Question 7

what are 2 examples of clinical relevance of Ca-calmodulin complex?

Answer 7

1) neurological disorders (needed in memory / learning)
2) cardio vascular health (muscle contraction)

Question 8

What is the primary function of inositol triphosphate (IP₃) in cellular signaling?

Answer 8

promotes Ca2+ release from the ER in response to extracellular signals

Question 9

what is the function of IP3? How is it generated in cells?

Answer 9

IP3 binds to receptors on the ER to signal Ca2+ release

1) A ligand (e.g., hormone, neurotransmitter) binds to a G protein-coupled receptor
2) phospholipase C (PLC) is activated and hydrolyzes PIP₂
3) PIP₂ is cleaved into two second messengers:
IP₃: Soluble and diffuses into the cytoplasm.
DAG: Remains in the membrane and activates protein kinase C (PKC).

Question 10

What are the two major ways calcium is removed from the cytoplasm?

Answer 10

Active Pumping into the Endoplasmic Reticulum (ER):
SERCA pumps restore calcium levels in the ER.

Extrusion from the Cell:
Calcium is expelled via plasma membrane calcium ATPases or sodium-calcium exchangers.

Question 11

What is the physiological importance of maintaining low cytoplasmic calcium levels?

Answer 11

High cytoplasmic calcium levels can cause:

1) Toxicity: Damage to organelles and enzymes.
2) Unregulated activation of signaling pathways, leading to apoptosis or necrosis.

Maintaining low levels ensures calcium acts as a precise second messenger.

Question 12

What are the chemical characteristics of phosphorus in the body? where is it stored? what state does it exist in? how is it impacted by its environment and what function does this serve in the body?

Answer 12

1) Most phosphorus in the body is stored in bone as hydroxyapatite
2) commonly exists as orthophosphate (HPO₄²⁻ and H₂PO₄⁻)
3) At pH 7.4, the HPO₄²⁻:H₂PO₄⁻ ratio is 4:1, making it an effective buffer.

Question 13

What are the biological functions of phosphate?

Answer 13

-bone mineralization
-electrolyte homeostasis (buffer)
-structural role (DNA/phospholipids)
-energy transfer (ATP,GTP,etc)
-second messenger (cAMP, IP3 pathways)
-metabolic regulation (phosphorylation/dephosphorylation)

Question 14

How does phosphate act as a physiological buffer?

Answer 14

The phosphate buffer system (HPO₄²⁻ ↔ H₂PO₄⁻) maintains intracellular and extracellular pH by donating or accepting H+

Question 15

what is the role of phosphate in DNA and RNA?

Answer 15

Phosphate alternates with pentose sugars (ribose / deoxyribose) to form the phosphate-sugar backbone of DNA and RNA

Question 16

What are the primary mechanisms of calcium absorption in the intestine?

Answer 16

1) Transcellular Pathway (major route):
Occurs in the duodenum.
Requires:
ATP and calbindin
-Stimulated by low Ca2+ diets and calcitriol (active vitamin D)
-saturatable

2) Paracellular Pathway (Passive):
Occurs in the jejunum and ileum.
Non-saturable, energy-independent, and depends on calcium concentration gradients

3) Colonic Fermentation:
Fermentation of dietary fiber in the colon releases small amounts of calcium

Question 17

how much of dietary Ca2+ is absorbed by colonic fermentation?

Answer 17

4-10%

Question 18

How does phosphorus absorption differ from calcium absorption?

Answer 18

-Phosphorus absorption is more efficient than calcium (60-70%).
-Occurs primarily as HPO₄²⁻.
-Unlike calcium, it is absorbed linearly with intake and is less dependent on vitamin D (calcitriol).

Question 19

what factors increase/decrease Ca2+ absorption?

Answer 19

increased Absorption:
1) Low calcium intake.
2) Elevated calcitriol
3) Estrogen and parathyroid hormone

Decreased Absorption:
1) High calcium intake.
2) Inadequate vitamin D.
3) Aging or postmenopausal status.

Question 20

what is PTH? what does it do? how does it do this? what are its target cells?

Answer 20

parathyroid hormone is a peptide hormone that acts on cell surface receptors. It increases blood calcium levels and decreases phosphate reabsorption through adenylate cyclase, cAMP and protein kinase

PTH is regulated by the parathyroid gland. It acts on:
kidney
-increase Ca reabsorption
-decrease phosphate reabsorption
-stimulates activation of calcitriol (Vit D)

Bone:
-stimulates osteoclasts to release Ca into blood

Intestine:
-Indirectly increases Ca absorption through Vit D activation

Question 21

What major hormones regulate calcium and phosphate metabolism? what do they do?

Answer 21

1) Parathyroid Hormone (PTH): Increases blood calcium levels, decreases phosphate reabsorption.

2) Calcitriol (Active Vitamin D): Enhances absorption of both calcium and phosphorus in the intestines.

3) Calcitonin: Decreases blood calcium levels by promoting bone mineralization and renal calcium excretion.

Question 22

what is the name of inactive vit D? what about active?

Answer 22

Inactive: 25 (OH) D or 25-hydroxyvitamin D
Active: 1,25(OH)2D, calcitriol, or dihydroxyvitamin D

Question 23

What is the role of calcitriol in calcium and phosphate homeostasis? how is it regulated?

Answer 23

Enhances absorption of Ca and phosphorous:

1) Increases calcium absorption in the intestine by upregulating calcium-binding proteins.
2) Enhances phosphate absorption by stimulating sodium-phosphate cotransporters.

Regulated by PTH, which stimulates calcitriol production in the kidney.

Question 24

what is the role of calcitonin in calcium homeostasis? how is it regulated?

Answer 24

Opposes PTH in order to decrease blood calcium levels by:

1) Inhibiting osteoclast activity → reducing bone resorption
2) Enhancing calcium excretion in the kidney
3) Decreasing intestinal calcium absorption

Released from the thyroid gland when calcium levels are high

Question 25

explain what happens when blood calcium levels are low.

Answer 25

Question 26

explain what happens when blood calcium levels are high.

Answer 26

Question 27

what is bone remodeling? what impact does it have on calcium levels? how does bone remodelling occur?

Answer 27

the replacement of bone mass (~10% every year) through repair and maintenance of blood calcium levels (helps prevent osteoporosis) 1) Osteoclasts: Break down bone, releasing Ca²⁺ & phosphate. 2) Osteoblasts: Build new bone, storing Ca²⁺ & phosphate.

Question 28

What are the phases of the bone remodeling cycle?

Answer 28

1. Activation (~40 days): Osteoclast precursor cells mature into active osteoclasts. 2. Resorption: Osteoclasts degrade bone, releasing minerals and matrix components. 3. Reversal (~145 days): Transition phase where mononuclear cells prepare for formation. 4. Bone Formation: Osteoblasts deposit osteoid and promote mineralization. 5.Mineralization: Osteoblasts become osteocytes, and hydroxyapatite forms.

Question 29

What is the role of osteoclasts in bone remodeling? what do they stimulate? what are they activated by?

Answer 29

1) Break down bone matrix using acidic enzymes. 2) Release calcium, phosphate, hydroxyproline, and collagen peptides into circulation. 3) Activated by RANKL, PTH, and inflammatory cytokines.

Question 30

What is the role of osteoblasts in bone remodeling?

Answer 30

Deposit new bone matrix

Question 31

what are pro-resorptive factors (bone breakdown)? what does this do to Ca? what type of cell is stimulated?

Answer 31

stimulate osteoclast activity, increasing Ca release: 1,25(OH)₂D (Active Vitamin D) Parathyroid Hormone (PTH) Inflammatory cytokines (IL-1, IL-6, TNF) Glucocorticoids (Cortis

Question 32

what are anti-resorptive (bone forming) factors?

Answer 32

Estrogens (inhibit osteoclast activity) Calcitonin (reduces calcium release from bone) Calcium availability

Question 33

what is RANKL and OPG? what do they do?

Answer 33

RANKL (Receptor Activator of Nuclear Factor Kappa B Ligand) Stimulates osteoclast differentiation and bone resorption OPG (Osteoprotegerin) Acts as a decoy receptor for RANKL, inhibiting osteoclast activation and preventing excessive bone resorption.

Question 34

How is calcium absorbed and excreted? what will increase/decrease absorption and excretion?

Answer 34

Absorption: ↑ Absorption with: Vitamin D (Calcitriol), proteins, sugars. ↓ Absorption with: Fiber, phytates, oxalates, high divalent cations (Zn, Mg) Excretion: ↑ Urinary excretion with: Sodium, caffeine, high-protein diet (due to sulfur AAs). ↓ Urinary excretion with: High phosphate (increases PTH, enhancing calcium reabsorption).

Question 35

How is phosphorus absorbed and excreted? what factors increase/decrease absorption and excretion?

Answer 35

Absorption: ↑ Absorption with: Vitamin D (Calcitriol). ↓ Absorption with: Phytates, excess Ca²⁺, Mg²⁺, Al³⁺ Excretion: ↑ Urinary excretion with: High phosphate, high calcium, PTH, estrogen, thyroid hormones. ↓ Urinary excretion with: Phosphate depletion, calcitriol, parathyroidectomy.

Question 36

how does excretion of Ca and phosphorous differ?

Answer 36

phosphorous excretion has a linear relationship with urine output unlike Ca2+ - kidneys regulate phosphate better

Question 37

What factors influence calcium bioavailability?

Answer 37

fibre, phytates, oxalates, protein

Question 38

What are the primary food sources of calcium?

Answer 38

Dairy products (milk, cheese, yogurt) = main dietary source in North America. Non-dairy sources: Some green vegetables (dependent on fibre content) Calcium-fortified foods (orange juice, cereals)

Question 39

How do calcium requirements change over the life cycle (general trends)? for infants (formula vs breast fed), puberty, post-menopausal and older adults?

Answer 39

Infants (0-12 months): Require high calcium retention for rapid bone growth Formula-fed infants: Lower calcium bioavailability due to lack of breast milk growth factors + phytates in soy formulas -more formula needed for similar amount Puberty: Peak calcium needs due to accelerated bone growth Post-menopausal women: Higher calcium needs due to estrogen deficiency → bone loss Older adults: Require increased intake to compensate for reduced absorption and prevent osteoporosis.

Question 40

what is the RDA of Ca for infants, children 9-18, adults, women >50 and pregnant women? what is the UL for 19-50 years?

Answer 40

infants: 200-260 9-18: 1300 19-50 and men >50: 1000 women > 50: 1200 pregnant: 1000 UL: 2500

Question 40

what is the trend of calcium intake vs DRI's over the life cycle?

Answer 40

increased requirments during growth periods decreased adequate intakes in the average population

Question 41

What are the major sources of dietary phosphorus?

Answer 41

Animal sources: Meat, poultry, fish, eggs, dairy (provide ~70% of phosphorus intake). Plant sources: Nuts, legumes, whole grains. Processed foods & sodas: Contain phosphorus additives (phosphoric acid).

Question 42

How do phosphorus requirements differ across life stages (general trends)? what is it based on?

Answer 42

Infants: AIs are based on average intakes of breastfed infants. Children: RDAs account for bone accretion and retention needs. Adults: RDAs based on serum phosphorus levels. No change for gender Pregnancy & Lactation: No evidence for increased requirements, as renal phosphorus recycling is efficient.

Question 43

What are the main causes of calcium deficiency?

Answer 43

1. Inadequate dietary intake (low dairy, low bioavailable sources). 2. Vitamin D deficiency (reduces intestinal calcium absorption). 3. Gastrointestinal disorders (Crohn’s, celiac disease → malabsorption). 4. Chronic kidney disease (CKD) (reduced vitamin D activation, increased calcium loss). 5. Hormonal imbalances (low estrogen, high PTH).

Question 44

How can you use serum calcium to indicate calcium status? explain what you expect when calcium levels are deficient.

Answer 44

you shouldnt, serum calcium levels are a poor indicator of calcium levles becuase it is tightly regulated by PTH, VIt D and calcitonin In deficiency, the body maintains normal levels by: 1)Increasing bone resorption (osteoclasts) 2)Reducing renal calcium excretion.

Question 45

what are good indicators of calcium levels?

Answer 45

Bone mineral density (DEXA scan), urinary calcium excretion, PTH levels.

Question 46

How does dietary calcium restriction affect the body?

Answer 46

↑ PTH secretion to maintain serum calcium. ↑ 1,25(OH)₂D (calcitriol) production to enhance calcium absorption. ↑ Bone resorption → Weakens bones, increases osteoporosis risk. ↓ Urinary calcium excretion to conserve calcium.

Question 47

What is hypercalcemia? what causes it? what are symptoms?

Answer 47

A condition where serum calcium exceeds 10.5 mg/dL. Usually caused by excessive bone resorption, increased calcium absorption, or decreased excretion. -muscle weakness, fatigue, depressed deep tendon reflexes

Question 48

what is hypocalcemia? what causes it? what are the symptoms?

Answer 48

serum calcium falls below 8.5 mg/dL. Can be caused by insufficient dietary calcium, vitamin D deficiency, or hormonal imbalances. -muscle spasm, numbness in fingers, face twitching

Question 49

What are the different types of osteoporosis? how do they differ? age, bone loss, fracture sites, causes and gender?

Answer 49

Postmenopausal Osteoporosis (Type I): Due to estrogen deficiency → Increased osteoclast activity. Affects mainly trabecular bone (spine, wrist fractures common). Age-Related Osteoporosis (Type II): Occurs in both sexes due to aging, reduced calcium absorption, and vitamin D deficiency. Affects both trabecular & cortical bone.

Question 50

What are the risk factors for osteoporosis?

Answer 50

Non-modifiable: Age, female sex, family history, menopause. Modifiable: Low calcium intake, vitamin D deficiency, smoking, alcohol, lack of weight-bearing exercise.

Question 51

Why is phosphorus deficiency rare?

Answer 51

1) Phosphorus is widely available in food (dairy, meat, grains, processed foods). 2) Kidneys efficiently regulate phosphorus balance by adjusting reabsorption.

Question 52

In what conditions does phosphorus deficiency occur?

Answer 52

Premature infants (breast milk may not meet high phosphorus needs). Chronic alcoholics (low intake, poor absorption, renal phosphate loss). Refeeding syndrome (rapid feeding after malnutrition → severe hypophosphatemia). Chronic kidney disease (CKD) (phosphate retention due to impaired excretion).

Question 53

What are the symptoms of phosphorus deficiency?

Answer 53

Muscle weakness (due to impaired ATP production). Bone pain (poor mineralization). Neurological dysfunction (confusion, irritability). Impaired oxygen delivery (due to reduced 2,3-BPG in red blood cells).

Question 54

How does phosphorus excess impact health?

Answer 54

Most harmful for people with kidney disease because they cannot excrete phosphorus, leading to: -Hyperphosphatemia. -Soft tissue calcification (vascular calcification, increasing cardiovascular disease risk). -Inhibited calcium absorption (promoting secondary hyperparathyroidism).