Calcium Homeostasis Flashcards
What is the importance of calcium distribution & balance?
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
What happens when Ca2+ deficiency occurs?
90% is absorbed from GIT
What are the major sources of calcium?
- 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
What is the importance of Nursing & pregnant mothers in relation to calcium homeostasis?
- 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
What 2 pools does Ca2+ exist in bone?
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
What factors alter blood Ca2+ levels?
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
What happens total Ca2+ levels fall?
- Nephrotic syndrome
- Malnutrition
- Liver disease
What happens when total Ca2+ levels increase?
Multiple myeloma
What is the importance of phosphate distribution and balance?
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
Summarize hormonal control of calcium
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
What is parathyroid hormone?
- 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+
What is the mechanism of PTH suppression?
- 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
What is the action of PTH on bone?
- 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.
What is the action of PTH on kidney?
- ↑ renal tubular reabsorption of Ca2+ in the distal tubules
- ↓ renal tubular reabsorption of PO4
• Indirectly increases intestinal absorption of Ca2+
-via vitamin D
What is the relation of vitamin D and PTH?
- 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
What is the role of Vitamin D action on the GIT?
Maintaining low intracellular calcium levels
Increasing calcium reabsorption by GIT
What is calcitonin?
- 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
What are the features of hypocalcemia?
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
What are the features of hypercalcemia?
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
In hyperparathyroidism…
Patients are said to have “stones, bones, groans and moabs”
What is primary hyperparathyroidism?
• 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”
What is secondary hyperparathyroidism?
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
What are the causes and characteristics of primary hyperparathyroidism?
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
What are rickets and osteomalacia?
• 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.
