Calcium Homeostasis

Question 1

What is the importance of calcium distribution & balance?

Answer 1

Ca2+ plays a central role in regulation of important cellular functions. The plasma concentration is 8.6 -10 mg/dl

• It accounts for 2% of the body weight. 99% Ca2+ is in bone & 1 % is in body fluids.

Note: The ionized form is physiologically active. Both ICF & ECF
Ca2+ in the plasma is tightly regulated

Question 2

What happens when Ca2+ deficiency occurs?

Answer 2

90% is absorbed from GIT

Question 3

What are the major sources of calcium?

Answer 3

• Major source of Ca2+ in the body is diet & bone. Milk, cheese & eggs are rich source of Ca2+
• If diet is deficient in Ca2+ it is absorbed from bone
• Kidney plays a major role in regulation of Ca2+ along with the bone
• Gut absorption, bone uptake & release, kidney Ca2+ reabsorption are tightly regulated to maintain Ca2+ within physiologic range

Question 4

What is the importance of Nursing & pregnant mothers in relation to calcium homeostasis?

Answer 4

• Nursing & pregnant mothers have high Ca2+ requirements
• About 625 mmols/day is absorbed via placenta for fetus, in pregnant mothers. Infants receive 2000 mmols/day via milk
• Fetus and infant, both need it for bone formation
• Ca2+ deficiency can occur in pregnant & nursing mothers

Question 5

What 2 pools does Ca2+ exist in bone?

Answer 5

Readily exchangeable pool (small reservoir) Slowly exchangeable pool (Stable pool)

• Bone is composed of organic matrix mostly collagen fibers 90 to 95%
• The rest is ground substance – ECF, proteoglycans, chondroitin sulfate & hyaluronic acid

Bone salts are deposited in the organic matrix mostly Ca2+ & PO4, MgSO4

Question 6

What factors alter blood Ca2+ levels?

Answer 6

At physiologic pH proteins are negatively charged. Changes in anions in plasma is also going to alter the plasma Ca2+ levels

• Increased or decreased plasma protein alters total Ca2+ levels
• For a change in 1g/dL of albumin concentration there is change 0.8 mg/dL of Ca2+ concentration

In clinical settings, it’s important to measure problems simultaneously with Ca2+ & PO4 level

Question 7

What happens total Ca2+ levels fall?

Answer 7

• Nephrotic syndrome
  
  • Malnutrition
  • Liver disease

Question 8

What happens when total Ca2+ levels increase?

Answer 8

Multiple myeloma

Question 9

What is the importance of phosphate distribution and balance?

Answer 9

Most of the dietary phosphate is absorbed. Serum concentration is 2.4 – 4.1 mg/dl

Typical daily exchanges of phosphorus
Phosphate distribution & balance
   86% is bone - in elemental form
•13 – 14% in ICF - organic form
 • very little in ECF
- inorganic form

Question 10

Summarize hormonal control of calcium

Answer 10

Ca2+ homeostasis is mainly regulated by parathyroid (PTH) hormone, & calcitriol or vitamin D3, calcitonin
• These hormones regulate via 3 organs, the intestines, kidneys & the bone
• Calcitonin is not important for Ca2+ regulation in humans, but important in fetus

Question 11

What is parathyroid hormone?

Answer 11

• PTH is an 84 amino acid peptide
• Is synthesized & stored in secretory granules
• It has a short half life 2- 4 minutes
• Rapidly removed from the kidney
• PTH is the most important regulator of ECF Ca2+

Question 12

What is the mechanism of PTH suppression?

Answer 12

• Free Ca2+ levels are sensed by a calcium-sensing receptor (CaSR) expressed by parathyroid chief cells, which synthesize PTH.
• CaSR is a GPCR encoded by the CASR gene.
• When CaSR binds Ca2+, it initiates Ca2+ release from intracellular stores and activates protein kinase C via Gαq and the IP3 signaling system

Question 13

What is the action of PTH on bone?

Answer 13

• PTH activates osteoclasts to increase bone resorption and the delivery of calcium from bone into plasma.
• PTH stimulates the maturation of immature osteoclasts into mature, active osteoclasts.

Question 14

What is the action of PTH on kidney?

Answer 14

• ↑ renal tubular reabsorption of Ca2+ in the distal tubules
• ↓ renal tubular reabsorption of PO4

• Indirectly increases intestinal absorption of Ca2+
-via vitamin D

Question 15

What is the relation of vitamin D and PTH?

Answer 15

• Vitamin D is a group of steroidal substances
• Binds to a nuclear vitamin D receptor (VDR). VDR complexes increases gene expression and protein synthesis
• Vitamin D3 (cholecalciferol) is important for Ca2+ homeostasis
  • formed in the skin
  • can be obtained from diet

Note: kidney failure thus may lead to hypocalcemia

Question 16

What is the role of Vitamin D action on the GIT?

Answer 16

Maintaining low intracellular calcium levels

Increasing calcium reabsorption by GIT

Question 17

What is calcitonin?

Answer 17

• Is secreted by C cells of the thyroid gland
• It is a 32 AA peptide, has a half-life of 5 mins
• Has opposite effect of PTH with respect to bone
• Helps in bone formation specially in fetus & neonates
• DOES NOT HAVE A MAJOR ROLE IN CALCIUM HOMEOSTASIS in humans

Question 18

What are the features of hypocalcemia?

Answer 18

Increases membrane excitability

• Paresthesias
• Hypocalcaemic tetany
• Chovstek’s sign twitching of facial muscles on tapping facial nerve*
• Trousseau’s sign when hand goes into tetany on inflating the BP cuff to systolic level*
• EKG shows prolonged QT interval

This induces PTH

Question 19

What are the features of hypercalcemia?

Answer 19

Nephrogenic DI (hypercalcemia) – polyuria, polydipsia)
• PUD (peptic ulcer disease) due to direct stimulation of parietal cells

• Urolithiasis or kidney stones (hypercalciuria)
• Neurologic symptoms i.e., psychiatric symptoms
• EKG shows shortened QT interval

Question 20

In hyperparathyroidism…

Answer 20

Patients are said to have “stones, bones, groans and moabs”

Question 21

What is primary hyperparathyroidism?

Answer 21

• Is usually due to

• parathyroid tumor
• ectopic parathyroid tissue

• Excess PTH causes

• increased serum Ca2+ & phosphaturia
• polyuria & calciuria & also forms kidney stones
• more prone peptic ulcer diseases - develop cystic lesions in the bone
• EKG shows shortened QT interval
• Patients are said to have “stones, bones, groans, and moans”

Question 22

What is secondary hyperparathyroidism?

Answer 22

Causes
- Diet deficient in Vitamin D
- Poor absorption of fat - vitamin D deficiency
- Inability to synthesize D3 - kidney disease
-increased Need for Ca2+ - pregnancy & lactation
• Is characterized by
-increased Serum PTH
-decrease To normal serum Ca2+ & decreased urine Ca2+
- decreased Serum phosphate levels but normal to increase urine phosphate levels

Question 23

What are the causes and characteristics of primary hyperparathyroidism?

Answer 23

Causes
- accidental removal of glands during thyroid or head & neck surgery
• Characterized by
- low Ca2+ & high plasma phosphate levels
- tetany (uncontrollable muscle contractions) is due to increase muscle excitability
• EKG shows prolonged QT interval
• ↓ Ca2+ < 6mg/ dl can lead to death

Question 24

What are rickets and osteomalacia?

Answer 24

• Causes due to Vitamin D deficiency
• There are ↓levels of Ca2+ & PO4 in ECF
• Characterized by demineralization of the osteoid matrix
- in children it is causes rickets
- in adults it leads to osteomalicia
 Rachitic Rosary – Vitamin D deficiency

Soft tissue overgrowth at costochondral junctions.