THE CALCIUM REGULATING HORMONES: PARATHYROID HORMONE

What are the 3 calcium-regulating hormones?

PTH, Calcitonin, and Vitamin D₃ (Calcitriol)

What is the main effect of PTH?

↑ Blood calcium + ↓ Blood phosphate

What is the main effect of Calcitonin?

↓ Blood calcium

What is the main effect of Vitamin D₃ (Calcitriol)?

↑ Intestinal absorption of calcium + phosphate

Why is ionized calcium important?

It is needed for muscle contraction, blood clotting, enzyme activity, and nerve function

What are the primary functions of calcium?

Structural support of bones and teeth + intracellular signaling

Where is 99% of calcium found?

In bone, stored as hydroxyapatite

Where is the remaining ~1% of calcium found?

In cells, mainly stored in the ER and cell membrane

How much calcium is found in extracellular fluid (ECF)?

About 0.1%

What are the 3 forms of calcium in blood?

Ionized, protein-bound, and complexed/anion-bound

What percentage of blood calcium is ionized?

About 50%

Can ionized calcium cross capillaries?

Yes

What percentage of blood calcium is protein-bound?

About 41%

Can protein-bound calcium cross capillaries?

No

What percentage of blood calcium is complexed/anion-bound?

About 9%

Can complexed calcium cross capillaries?

Yes

What is ionized calcium?

The free and active form of calcium that produces physiologic effects

What is protein-bound calcium mainly bound to?

Albumin

Is protein-bound calcium active?

It is considered inactive

Can protein-bound calcium be filtered by the kidney?

No

What is complexed calcium bound to?

1. Phosphate

2. Citrate

3. Bicarbonate

4. Lactate

Can complexed calcium be filtered?

Yes, it is filterable

What is ultrafilterable calcium?

Ionized + complexed calcium

Which forms of calcium enter the glomerulus during filtration?

Ionized and complexed calcium

Which form of calcium does not enter the glomerulus during filtration?

Protein-bound calcium

What is the normal extracellular calcium concentration?

About 1.2 mmol/L

What is the approximate intracellular calcium concentration?

About 100 nM

How large is the calcium concentration gradient across the cell membrane?

About a 10,000-fold difference

Why is there a large calcium gradient across cell membranes?

It allows calcium to act as an intracellular signal

What regulates calcium entry into cells?

1. Membrane Potential

2. Cell Receptors/Second Messengers

What does calcium inside cells cause?

1. Neurotransmitter Release

2. Muscle Contraction

3. Hormone Secretion

4. Activation of Calmodulin + Protein Kinases

Why is low intracellular calcium normally important?

Cells normally maintain very little calcium inside to allow calcium to function as a controlled intracellular signal

What happens to intracellular calcium during cell injury?

With anoxia, ATP depletion, or membrane damage, excess calcium enters the cell

What happens when excess calcium enters an injured cell?

It causes cell damage and cell death

How much filtered calcium do the kidneys reabsorb?

≥98%

How much filtered calcium is normally excreted?

About 2%

What percentage of calcium is reabsorbed in the PCT?

About 70%

How is calcium reabsorbed in the PCT?

Mostly passively through diffusion and water movement

What percentage of calcium is reabsorbed in the thick ascending loop?

About 20%

How is calcium reabsorbed in the thick ascending loop?

Mostly passively

What percentage of calcium is reabsorbed in the DCT?

About 10%

How is calcium reabsorbed in the DCT?

Actively, stimulated by PTH

What does active calcium reabsorption in the DCT require?

1. Calcium Channels

2. Calbindin

3. Ca-ATPase

4. Na/Ca Exchanger

What does the Ca/creatinine ratio correct for?

1. Collection Timing

2. Urine Dilution

3. Muscle Mass

When is fractional calcium excretion best measured?

Fasting

What does fractional calcium excretion reflect?

1. Bone Calcium Release

2. Normal Kidney Calcium Loss

What does 24-hour urine calcium measure?

Total daily calcium loss

What are the 2 pathways of intestinal calcium absorption?

1. Transcellular

2. Paracellular

What is transcellular calcium absorption?

Calcium absorption through intestinal cells

Is transcellular calcium absorption vitamin D dependent?

Yes

Is transcellular calcium absorption saturable?

Yes

Where does transcellular calcium absorption occur mainly?

In the duodenum

What does transcellular calcium absorption require?

1. Calcium Channels

2. Calbindin

3. Ca-ATPase

What is paracellular calcium absorption?

Calcium absorption between intestinal cells

Is paracellular calcium absorption active or passive?

Passive

Where does paracellular calcium absorption occur?

Throughout the intestine

When is paracellular calcium absorption especially important?

During vitamin D deficiency

How much calcium can be absorbed on a low-calcium diet?

Up to 95%

How much calcium is absorbed on a high-calcium diet?

About 40%

How does the body regulate calcium absorption according to dietary calcium?

It adjusts the percentage absorbed according to need

When does increased calcium absorption occur?

During growth, pregnancy, lactation, and low-calcium diets

What is the main regulator of increased intestinal calcium absorption?

1,25-dihydroxyvitamin D (calcitriol)

What hormones increase calcium absorption?

PTH, growth hormone, testosterone, estrogen, and furosemide indirectly

What factors decrease calcium absorption?

Glucocorticoids, thyroid hormones, chronic acidosis, high phosphate, phytates, oxalates, fatty acids, and pH >6

What are the 2 major calcium stores in bone?

1. Calcium Salts

2. Hydroxyapatite

What is the easily mobilized calcium store?

Calcium salts associated with the ECF

What is the major calcium storage in bone?

Hydroxyapatite

What cells are required to mobilize the major hydroxyapatite calcium store?

Osteoclasts

What is calcium balance in adult animals?

Bone formation = bone resorption

What is calcium balance in young animals?

Bone formation > bone resorption, producing a positive calcium balance

What does excess bone resorption cause?

Hypercalcemia

What conditions are associated with excess bone resorption?

1. Humoral Hypercalcemia of Malignancy

2. Osteolytic Metastasis

3. Primary Hyperparathyroidism

What is the calcium-sensing receptor (CaSR)?

A receptor that detects blood calcium

Where is CaSR mainly located?

In the parathyroid gland and kidney

Where else is CaSR found?

Thyroid C cells, brain, and placenta

What does CaSR control?

1. PTH + Calcitonin Secretion

2. Renal Calcium Handling

Where is 90% of phosphate found?

In bone

Where is the remaining 10% of phosphate found?

In soft tissues

What is the major intracellular anion?

Phosphate

What are the 2 forms of inorganic phosphate?

HPO₄²⁻ and H₂PO₄⁻

What are examples of organic phosphate?

1. ATP

2. DNA/RNA

3. Phospho (-lipid, -protein)

What are the major functions of phosphate?

1. ATP Production

2. Oxygen Delivery

3. Muscle Contraction

4. Bone Mineralization

5. Rapid shifts between cells and blood.

What percentage of dietary phosphate is absorbed?

About 60–70%

What are the mechanisms of phosphate absorption?

Na/Phosphate Cotransport + Passive Diffusion

Where is phosphate absorbed in ruminants?

The forestomach

Where is phosphate absorbed in monogastrics?

The duodenum and jejunum

Where is phosphate absorbed in horses?

The large intestine

What increases intestinal phosphate absorption?

Vitamin D

What happens when dietary phosphate is low?

The body increases intestinal absorption, calcitriol production, and kidney phosphate reabsorption

What factors reduce phosphate bioavailability?

Aluminum, magnesium, and high calcium + fat

What is phytate?

The main phosphorus form in plant feeds

How well do ruminants digest phytate?

They digest it well because of rumen phytase

How well do nonruminants digest phytate?

They digest it poorly

What improves phytate phosphorus absorption in nonruminants?

Microbial phytase

Why does ruminant saliva contain large amounts of phosphate?

Buffers rumen acids + feeds rumen microbes

What happens to saliva and fecal phosphate loss on a high-fiber diet?

↑ Saliva and ↑ fecal phosphate loss

What happens to saliva and urinary phosphate on a concentrate diet?

↓ Saliva and ↑ urinary phosphate

Where does most renal phosphate reabsorption occur?

The PCT

Where does a small amount of phosphate reabsorption occur?

The DCT

What is required for renal phosphate reabsorption?

Sodium