Quiz 9: Biomedical Sciences

What are the three main tissues that regulate Ca and P balance in the body?

GI tract (absorption), kidney (reabsorption/excretion), and bone (storage and release)

Which hormones regulate Ca and P homeostasis?

parathyroid hormone (PTH), calcitriol (active vitamin D), and FGF23 (mostly for P)

Calcitonin exists but has minimal physiologic relevance.

What is the overall goal of Ca/P homeostasis?

maintain tight serum levels through balanced intake, storage, and excretion

Which hormones are physiologically most important for calcium regulation?

PTH and calcitriol

Calcitonin is not physiologically essential

What are the major functions of calcium in the body?

- bone/teeth formation

- muscle and cardiac contractility

- neurotransmission

- blood coagulation

What are the major functions of phosphorus in the body?

- bone/teeth formation

- ATP production (energy)

- nucleic acids

- cell membrane structure (phospholipids)

- regulatory functions

Why are small serum calcium changes clinically significant?

it affects critical systems like neuronal excitability, cardiac rhythm, muscle contraction. Even slight imbalance causes dysfunction

What disease is caused by vitamin D deficiency in children leading to bone softening?

rickets

What are symptoms of hyperparathyroidism?

kidney stones, bone loss (osteoporosis), and muscle weakness

What disorders involve excessive bone resorption?

osteoporosis, Paget's disease, and hyperparathyroidism

What symptoms occur in hypoparathyroidism?

tetany, heart block, neuromuscular excitability

What is the key for balance in whole-body calcium turnover?

dietary intake must equal urinary and fecal losses, with bone as major storage

What organ filters the most calcium daily, and what percent is reabsorbed?

the kidney; over 98% of filtered calcium is reabsorbed

Why is renal excretion of calcium important despite low amounts?

even small changes in urinary calcium significantly affect serum Ca balance

Which 3 tissues does PTH target?

bone (increase resorption), kidney (increase reabsorption), GI tract indirectly via calcitriol

How does calcitriol indirectly influence calcium?

it increases calcium absorption from the GI tract

How does PTH affect phosphate levels?

it decreases phosphate by inhibiting reabsorption in the kidney

What determines bone density?

balance between osteoclast-mediated resorption and osteoblast-mediated bone formation

Which cell type releases calcium from bone?

osteoclasts

Which cell type builds new bone and sequesters calcium?

osteoblasts

What are the three key proteins required to absorb calcium through intestinal cells?

TRPV channels, Calbindin, and PMCA (plasma membrane calcium ATPase)

What is the role of calbindin in enterocytes?

binds calcium and shuttles it across the cell to prevent toxicity and allow transport to blood

What is the big-picture concept behind intestinal Ca absorption?

hormone-regulated expression of transport proteins moves calcium THROUGH the enterocyte into blood

Which three proteins are required for renal calcium reabsorption in the distal tubule?

TRPV channels (5 and 6), Calbindin, and PMCA (plasma membrane calcium ATPase)

What hormone stimulates renal expression of TRPV5/6, Calbindin, and PMCA?

Parathyroid hormone (PTH)

Where does hormonally regulated calcium reabsorption mainly occur in the kidney?

distal convoluted tubule

Where is the parathyroid gland located?

posterior to the thyroid gland in the neck

Is PTH a peptide, steroid, or amine hormone?

PTH is a peptide hormone

What is the effect of PTH on bone?

increases bone resorption, activates osteoclasts, and releases Ca²⁺ and phosphate into blood

What is the effect of PTH on calcium in the kidney?

increases calcium reabsorption by upregulating TRPV, Calbindin, and PMCA

How does PTH affect phosphate in the kidney?

inhibits phosphate reabsorption (promotes phosphate excretion)

What enzyme does PTH stimulate in the kidney?

1-alpha-hydroxylase (converts vitamin D to calcitriol)

What is the strongest stimulus for PTH secretion?

decreased serum ionized calcium

What two signals decrease PTH secretion?

increased serum calcium and high calcitriol levels

How does calcitriol decrease PTH production?

directly suppresses PTH gene transcription in the parathyroid gland

How does PTH secretion respond to small changes in ionized calcium?

PTH release changes drastically in response to even small calcium fluctuations, demonstrating tight regulation

What type of feedback regulates PTH release by calcium?

negative feedback (higher calcium suppresses PTH)irect negative feedback — decreases PTH gene transcription

How does ionized calcium inhibit PTH secretion at the cellular level?

calcium binds to Ca-sensing receptors on parathyroid cells → inhibits PTH gene transcription and secretion from granules

What happens when Ca-sensing receptors are unactivated (low Ca²⁺)?

PTH secretion increases

What happens when PTH binds to distal tubular cells?

it stimulates expression of TRPV channels, Calbindin, and PMCA for Ca²⁺ reabsorption

Why is renal calcium reabsorption vital to PTH function?

prevents excessive calcium loss in urine and defends plasma Ca²⁺ levels

What is the first rapid response to reduced plasma calcium?

rapid release of calcium from the labile pool in bone (independent and PTH-stimulated)

What is the slow response to low serum calcium?

PTH stimulates osteoclasts to resorb bone and produce calcitriol → increasing GI absorption of calcium

How does PTH prevent calcium-phosphate precipitation?

inhibits phosphate reabsorption → lowers serum phosphate → prevents Ca-P complex formation

Which processes are rapid in PTH response?

bone labile Ca release, renal Ca reabsorption, and phosphate excretion

Which processes are slow in PTH response?

osteoclastic bone resorption and calcitriol-mediated GI absorption

Why is calcitriol activation slow?

it requires kidney conversion via 1-alpha-hydroxylase and acts through gene expression changes

Where is most phosphorus stored in the body, and in what form does it circulate in blood?

~85% in bone; circulates as phosphate (HPO₄²⁻ / H₂PO₄⁻)

What are the three main hormones regulating phosphorus homeostasis?

PTH, FGF23, and calcitriol

What are the two major hormone target organs for phosphorus regulation?

kidney (elimination) and GI tract (absorption)

- bone is minor

What is the primary mechanism for regulating serum phosphorus?

renal phosphate excretion (proximal tubule)

How does PTH affect phosphate in the kidney?

inhibits phosphate reabsorption by degrading Type IIa transporters on urine side

How does FGF23 regulate phosphate?

decreases calcitriol synthesis and inhibits both uptake and efflux of phosphate in kidney

What stimulus causes bone to release FGF23?

high serum or dietary phosphate

How do PTH and FGF23 interact in phosphate regulation?

both inhibit phosphate reabsorption in kidney, but have opposite effects on calcitriol

Which hormones stimulate 1α-hydroxylase?

PTH, estrogen, low Ca²⁺/P

Which hormones inhibit 1α-hydroxylase?

FGF23 and calcitriol (self)

What is the precursor of vitamin D, and what activates it?

cholesterol; activated by UV light in skin → Vitamin D₃ → liver (25-OH) → kidney (calcitriol)

How does calcitriol affect the parathyroid gland?

direct negative feedback → decreases PTH gene transcription

How do PTH, calcitriol, and FGF23 coordinate?

PTH: ↑ Ca, ↓ phosphate

Calcitriol: ↑ Ca & phosphate (GI)

FGF23: ↓ phosphate & ↓ calcitriol

**Together maintain Ca/P balance

How does chronic kidney disease (CKD) affect Ca/P homeostasis?

reduces calcitriol production and phosphate excretion → ↑ PTH (secondary hyperparathyroidism)