Calcium HomeostasisPRAKASH POKHREL

Outline

Introduction Calcium metabolism - PTH, Calcitonin, Vitamin d Functions of calcium Disorders of calcium Summary

Introduction

Total plasma [Ca++] = 2.5mmol/L Range is 2.1 to 2.6 mmol/L Very tightly controlled

Body content

Bone intracellular

extracellular

Calcium 1300 gm 99% 1% 0.1%

Introduction

Factors affecting calcium concentration

1) Changes in plasma protein concentration- Increased [protein] – increased total [Ca2+]

2) Changes in anion concentration- Increased [anion] – increased fraction of Ca2+ that

is complexed – decrease ionized [Ca2+]

3)Acid base abnormality

Acid Base Abnormality

Functions of Calcium

1. Nerve and muscle functions- Decreased extracellular calcium – increase

excitability of excitable cells and lowers the threshold potential – less inward current is required to depolarize the threshold potential – less inward current is required to fire AP

- Hence causing tingling and numbness (sensory) and spontaneous muscle twitches (motor neurons and muscles)

Functions of Calcium 2. Homeostasis-activation of clotting enzyme is the plasma

Functions of Calcium

3. Preserving bone density- construction, formation and maintenance of bone

and teeth. This function helps reduce the occurrence of osteoporosis

Functions of Calcium

4. Neurotransmitter release- Directly proportional to the calcium level- Arrival of action potential to axonal terminal opening of voltage gated calcium channels calcium influx into the terminal transmitter

vesicle fuse with the release sites exocytosis-release of transmitters into the cleft

Functions of Calcium

5. Calcium assists in maintaining all cells and connective tissues in the body and regulating mitotic transition and cell division.

6. Essential component in the production of enzyme and hormones that regulate digestion, energy, and fat metabolism.

Calcium Homeostasis

Blood calcium is tightly regulated by:

1) Principle organ systems: IntestineBoneKidney

2) Hormones: Parathyroid hormone (PTH)Vitamin DCalcitonin

Calcium Homeostasis

Parathyroid Hormone (PTH)

There are 4 parathyroids glands, located on the dorsal side of the thyroid

The blood supply to the parathyroid glands is from the thyroid arteries.

Parathyroid Hormone (PTH)

• Chief cells secrete PTH• Oxyphil cells – function unknown. Probably degenerated chief cells.

Parathyroid Hormone (PTH)

Regulation of PTH by plasma calcium concentration

Parathyroid Hormone (PTH)

Mechanism Increase in extracellular calcium concentration

Ca2+ binds to the receptor and activates phospholipase C increased levels of IP04/Ca2+ which inhibits PTH secretion.

When extracellular Ca2+ is decreased, there is decreased Ca2+ binding to the receptor, which stimulates PTH secretion.

Parathyroid Hormone (PTH)

Actions of PTH on bone, kidney and small intestine Direct vs indirect

1) Actions on bone- PTH receptors on osteoblasts – initial bone

formation (direct action)- Later on – bone resorption (indirect action) via

cytokines from osteoblast- Overall effect : promote bone resorption and

increase calcium concentration

Parathyroid Hormone (PTH)

a) Inhibits PO4 reabsorption (inhibits Na-PO4 cotransport in PCT) – phosphaturia – less complexed Ca-PO4 – increase plasma calcium

b) Stimulates calcium reabsorption (on DCT)

Phosphaturia + Ca2+ reabsorption = increase in Ca2+ concentration

Parathyroid Hormone (PTH)

3. Actions on small intestine (indirect)- Stimulates Ca2+ reabsorption via activation of vitamin D.- PTH stimulates renal 1 alpha hydroxylase converts 25-hydroxycholecalciferol to 1,25 dihydroxycholecalciferol stimulates intestinal Ca2+ absorption

Parathyroid Hormone (PTH)

Vitamin D

Vitamin D

Actions of vitamin D

Vitamin D

Common diseases related to vitamin D1) Rickets - insufficient amounts of calcium and

phosphate to mineralize the growing bones growth failure and skeletal deformities

2) Osteomalacia – new bone fails to mineralize bending and softening of weight bearing bones

Calcitonin

a straight-chain peptide with 32 amino acids. synthesized and secreted by the parafollicular cells of the thyroid

gland. major stimulus for calcitonin secretion is increased plasma Ca2+

concentration The major action of calcitonin is to inhibit osteoclastic bone

resorption, which decreases the plasma Ca2+ concentration. calcitonin does not participate in the minute-to-minute regulation

of the plasma Ca2+ concentration in humans. a physiologic role for calcitonin in humans is uncertain because

neither thyroidectomy (with decreased calcitonin levels) nor thyroid tumors (with increased calcitonin levels) cause a derangement of Ca2+ metabolism, as would be expected if calcitonin had important regulatory functions.

Calcium handling in the nephron

Calcium handling in the nephron

- 67% of the filtered load is reabsorbed @ PCT- Ca2+ reabsorption is tightly coupled to Na+

reabsorption in the proximal tubule

Calcium handling in the nephron

- @ ALH , 25% of the filtered load of Ca2+ is reabsorbed - The mechanism of coupling in the thick ascending limb depends on

the lumen-positive potential difference, which is generated by the Na+-K+-2Cl- cotransporter.

- Loop diuretics such as furosemide inhibit Ca2+ reabsorption to the same extent that they inhibit Na+ reabsorption.

Calcium handling in the nephron

@ DT 8% of the filtered load of Ca2

the site of regulation of Ca2+ reabsorption. the distal tubule is the only nephron segment in which Ca2+ reabsorption

is not coupled directly to Na+ reabsorption. it has its own regulatory hormone, PTH. Thiazide diuretics increase Ca2+ reabsorption, while the other classes of

diuretics decrease it.

Hypocalcaemia

Symptoms and signs "CATS go numb"- Convulsions, Arrythmias, Tetany

and numbness/parasthesias in hands, feet, around mouth and lips.

Trousseau sign of latent tetany (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic)

Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms

Hypercalcemia

Causes

Hypercalcemia

"Stones, Bones, Groans, Thrones and Psychiatric Overtones“

-Stones (renal or biliary)

-Bones (bone pain)

-Groans (abdominal pain, nausea and vomiting)

-Thrones (sit on throne - polyuria)

-Psychiatric overtones (Depression 30-40%, anxiety, cognitive dysfunction, insomnia, coma)

Summary

Calcium is crucial for body physiological function It must be tightly regulated to maintain

physiological stability, by the interaction between the major organs (Intestine, kidney, bone) and hormones ( PTH, Calcitonin, Vitamin D)

Summary

A decrease in calcium level – stimulate PTH release – increase bone reabsorption, increase Ca2+ reabsorption from kidney (DCT), decrease PO4 reabsorption from kidney (PCT), and increase calcium uptake from GI (indirect)

Vitamin D – same action but increase PO4 reabsorption from kidney

Calcium imbalance must be recognized and treated early to prevent any catastrophe.

Reference

Physiology by Linda S. Costanzo 3rd edition