Calcium Homeostasis Flashcards by Rhiannon Price

How is calcium stored?

Majority (99%) of calcium is stored within bone as extracellular matrix
1% of body calcium in soluble form in extracellular fluids and in cells

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How is calcium transported in the blood?

40% bound to plasma proteins
10% in complexes (citrate, phosphate)
50% in an ionized (active) form

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Where do the calcium buffers lie?

Exchangeable calcium in bone salts

Exchangeable calcium in mitochondria

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If an animal is hypocalcemic and needs more calcium what hormones are produced?

Increase parathyroid hormone (PTH)

Produce more activated vitamin D3

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If an animal is hypercalcemic and needs more calcium what hormones are produced?

Decrease parathyroid hormone (PTH)

In severe hypercalcemia Calcitonin

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PTH is secreted by what cells?

Secreted by the principal (chief cells) of the parathyroid glands

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How is PTH synthesised?

Starts as a Pre-prohormone of 110 amino acids
Then into a prohormone of 90 amino acids
Finally into secretory vesicles as PTH, with a length of 84 amino acids
First 34 amino acids (N-terminus) mediates the actions

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What is the half life of PTH and where is it degraded?

Short half-life of 10 minutes

Degraded in the liver

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PTH secretion is fine tuned by…

Negative feedback at the level of the principle cells via the Receptor coupled to G protein which controls exocytosis of PTH containing vesicles

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How does PTH increase calcium levels?

Bone: Fast (min) phase from bone fluid
Bone: Slow (days) phase from bone
Kidney: Reabsorption within tubules
Intestine: Indirect effect through the activation of vitamin D

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How is calcium reclaimed from the bone matrix?

Osteoclasts (multinucleated) erode bone and incorporate calcium into ECF

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What is the osteocytic membrane and what does it do?

There is a continuous layer of osteocytes and osteoblasts that covers bone surface provides a physical barrier between the bone and the extracellular fluid of the body

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Where is the bone fluid?

Bone fluid between the osteocytic membrane and the bone

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How fast is fast bone phase of calcium reabsorption?

Begins in minutes and progressively increases for hours

Increased calcium uptake from bone fluid

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How does PTH regulate calcium uptake from bone fluid?

PTH interacts with membrane receptors on osteocytes and osteoblasts
Increases permeability to calcium on bone fluid side of the membrane
Increased calcium uptake from bone fluid
Bone fluid calcium level drops
Nearby calcium phosphate crystals replace calcium in the bone fluid (osteolysis)

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How does PTH cause the slow uptake of calcium from bone

Activation of osteoclastsand formation of new osteoclasts
No receptors for PTH, so signal comes from activated osteocytes and osteoblasts
Takes days (48 hours) to respond
Progressive depletion of bone mineral

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How does PTH cause calcium retention in the kidneys?

Increases calcium reabsorption in the late distal tubules and collecting tubules
Results in retention of Ca and Mg
Decreases phosphorous reabsorption in the renal proximal tubule
Results in rapid loss of phosphorous

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How does PTH cause activation of vitamin D (calcitriol)?

Vitamin D from the diet or skin
Final conversion to active vitamin D (calcitriol) occurs in the kidney
Catalyzed by the enzyme: 1-alpha-hydoxylase
This enzyme is activated by PTH

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What does calcitriol do?

Calcitriol (active vitamin D) increases the active transport of calcium

How does calcitriol cause an increase in calcium absosrbtion in the GI tract?

Calcitriol Enters intestinal epithelial cells and Increases the synthesis of calcium-binding protein (calbindin)
Takes approximately 48 hours (slow)
Accelerated by calcitriol-activated calcium ATPase pumps on the basolateral membranes (secondary active transport)
Calcium-binding protein (calbindin) ferries calcium from apical region to the pumps

How else does calcitriol increase the calcium levels?

Decreases calcium excretion by the kidneys
Affects renal tubular epithelial cells
Increase calcium (and phosphorous) reabsorption from urine
WEAK effect in comparison with PTH

What stimulates calcitonin?

Stimulated by hypercalcemia

What are the effects of calcitonin?

Opposite effects to PTH on the bone
Bone: Rapid (min) phase into bone fluid
Bone: Slow (days) phase into bone

Slight (insignificant) effects on the kidney and intestinal tract

What is the second most abundant intracellular ion and where is it found?

Mg found in blood

Why is Mg important?

Important co-factor for enzymes Pumps depend upon Mg e.g. Na-K ATPase ATP production and nucleic acid synthesis

Is Mg hormonally controlled?

How is increased influx of Mg handled?

easily handled via excretion through saliva, urine and milk

Is excess Mg loss handled well?

What does hypocalcemia cause? What are the knock on effects of this?

It overall reduces muscle contractility so: This reduced muscle contractility will have a knock on effect on posture (recombancey and S bend neck) Repro: dystocia caused by a lack of uterine contractility (this can also cause a retained placenta)there is a slow return to cyclicity and potentially uterine prolapse GI: low rumen contractility or gassy bloat Cardiac: slightly tachycardic, cold extremities (hence don’t treat sub cut as it won’t absorb as well)

A cow in full milk will require how many extra grams of Ca?

73g on top of 25g maintenance

What secondary conditions will impair a cows response to PTH and potentially cause hypocalcaemia?

Metabolic alkalosis at calving reduces response to PTH | Insufficient Mg reduces PTH secretion and effect

What do dogs and horses get when they have low calcium?

Tetany (stiffness) rather than paresis

What is metabolic bone disease in reptiles?

This is a secondary nutritional hyperparathyroidism as they mobilise a lot of calcium from their bone matrix and cause pathological fractures Reptiles also have tetany rather than paresis

Calcium is decreased by ..................

Calcitonin | Produced by Parafollicular cells (C-cells) of thyroid

Calcium is increased by ....................

Active vitamin D3 (calcitriol) | Activated in the kidney and acts to increase gut absorption

What are the 4 main physiological causes hypercalcaemia?

1. Increased PTH 2. Production of PTH related peptide (PTHrp) 3. Increased vitamin D3 (toxicosis) 4. Decreased urinary excretion of calcium

What is PTH-related protein?

Identical biological activity as PTH Not detected by PTH assay (as it has -COOH end) Produced by Cartilage, bone, muscle, epithelium, CNS

What are the HOGS IN YARD causes of hypercalcaemia?

``` H - Hyperparathyroidism O - Osteolysis G – Granulomatous Disease S – Spurious (Albumin?) I - Idopathic N - Neoplasia Y - Young A – Addison’s Disease R – Renal Disease D – Vitamin D Toxicity ```

What are the top 3 causes of hyperC in dogs?

Malignancy Hypoadrenocorticism Primary hyperparathyroidism

What are the top 3 causes of hyperC in cats?

Idiopathic Renal failure Malignancy

What are the top 3 causes of hyperC in horses?

Chronic renal failure Vitamin D toxicity Malignancy

What are the clinical signs of hyperC

PU/PD Anorexia, vomiting, constipation (due to decrease in GI muscle excitability) Muscle twitching, shivering, seizures Bradycardia, cardiac arrhythmias Soft tissue mineralization (if P is high)

How does a neoplasia cause hyperC?

PTHrp production by neoplasia

What is primary hyperparathyroidism?

Abnormality of principal cells | Gland functions autonomously and does not respond to increase in calcium

How does renal failure cause rubber jaw?

Decreased GFR, decreased reabsorbtion of Ca, Increased PTH to maintain Ca which leads to fast and slow retrieval of Ca from bone and causes fibrous osteodystrophy