Calcium Homeostasis Flashcards
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
How is calcium transported in the blood?
40% bound to plasma proteins
10% in complexes (citrate, phosphate)
50% in an ionized (active) form
Where do the calcium buffers lie?
Exchangeable calcium in bone salts
Exchangeable calcium in mitochondria
If an animal is hypocalcemic and needs more calcium what hormones are produced?
Increase parathyroid hormone (PTH)
Produce more activated vitamin D3
If an animal is hypercalcemic and needs more calcium what hormones are produced?
Decrease parathyroid hormone (PTH)
In severe hypercalcemia Calcitonin
PTH is secreted by what cells?
Secreted by the principal (chief cells) of the parathyroid glands
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
What is the half life of PTH and where is it degraded?
Short half-life of 10 minutes
Degraded in the liver
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
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
How is calcium reclaimed from the bone matrix?
Osteoclasts (multinucleated) erode bone and incorporate calcium into ECF
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
Where is the bone fluid?
Bone fluid between the osteocytic membrane and the bone
How fast is fast bone phase of calcium reabsorption?
Begins in minutes and progressively increases for hours
Increased calcium uptake from bone fluid
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)
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
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
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
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?
No
How is increased influx of Mg handled?
easily handled via excretion through saliva, urine and milk
Is excess Mg loss handled well?
No
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?
- Increased PTH
- Production of PTH related peptide (PTHrp)
- Increased vitamin D3 (toxicosis)
- 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
