Calcium and phosphorus homeostasis Flashcards
Important factors in calcium homeostasis
Parathyroid hormone
Vitamin D
Calcitonin
PTHrP
Renal function
What do PTH and vitamin D alter to regulate calcium levels?
Renal reabsorption and loss
Uptake and loss of calcium from bone
Gut uptake and loss of calcium from bone
Action of calcitonin
Acts on bone to prevent calcium mobilisation through osteoclastic activity
PTHrP
PTH-like factor
Important role in mediating hypercalcaemia of malignancy
Involved in calcium regulation in the foetus and is also secreted into milk so role in neonate
In malignancy PTHrP can mimic the action of PTH
Phosphate
Most abundant intracellular anion.
80-85% stored as hydroxyapatite in bone, 15% in soft tissues such as muscle.
Vitamin D promotes calcium and phosphate uptake in the gut.
Hyperphosphataemia
Occurs most commonly with renal insufficiency
Causes of hypophosphataemia
Shift into intracellular space
- insulin therapy
- IV glucose administration
- Respiratory alkalosis
- Metabolic acidosis
Increased urinary excretion
E.g. DM, hyperparathyroidism etc.
Decreased gut absorption
E.g. decreased intake, malabsorption
Differential diagnoses of hypercalcaemia in dogs
Most commonly malignancy
- Lymphoma
- Anal sac adenocarcinoma
- Multiple myeloma
- Etc.
Primary hyperparathyroidism
Hypoadrenocorticism (Addisons)
Chronic renal failure
Vitamin D intoxication
Granulomatous disease
Parameters of primary hyperparathyroidism
Increased total calcium, ionised calcium, and PTH
Decreased phosphate
Normal PTHrP
Parameters of secondary renal hyperparathyroidism
Total calcium increased, normal, or decreased
Ionised calcium decreased or normal
Increased phosphate
PTH increased or high normal
PTHrP normal or increased
Hypervotaminosis D
Iatrogenic (cod liver oil)
Plants (calcitriol glycosides)
Rodenticides (cholecalciferol)
Anti-psoriasis creams (calcipotriol or calcipotriene)
Idiopathic hypercalcaemia in catz
Most common cause of ionised hypercalcaemia in cats
Clinical signs mild or none
PTH, PTHrP and calcitriol suppressed in most
Renal function is normal, at least initially
Calcium oxalate uro lithuania is common
Causes of IHC in cats
Unknown
Inappropriate dietary vit D may play a role
Mutations in vit D receptors
Other genetic causes
Management of idiopathic hypercalcaemia in cats
Diurese using normal saline
Diet
- high fibre
- renal
- diets for calcium oxalate urolithiasis
Steroids (preds)
- decreases absorption and resorption, and skeletal mobilisation
Bisphosphonates
- reduce activity and no of osteoclasts
Calcimimetics
- lower iCa, phosphorus, and PTH concentrations
Primary hyperparathyroidism in dogs
Usually occurs in middle-older aged dogs (8-12yrs, mean 11.2yrs)
Onset of disease can be slow and insidious and is often ignored as part of the normal aging process
Many dogs diagnosed when being investigated for other conditions or when undergoing health checks
Clinical signs may be mild or not perceived to be present at all
Keeshonden have the highest breed predisposition
Clinical signs of Primary hyperparathyroidism in dogs
Mild to moderate hypercalcaemia may cause no obvious clinical signs
Can cause PU/PD
Muscle weakness and exercise intolerance
Inappetence and weight loss
Constipation
Facial pruritus and oral discomfort
Calcium-containing urolithiasis
Renal failure
Diagnosis of Primary hyperparathyroidism in dogs
Demonstration of hypercalcaemia alongside hyperparathyroidism
Both total and ionised calcium will be elevated
Phosphate low or low normal
PTHrP will be normal
Survey radiographs for neoplasia often unremarkable
Cervical ultrasound examination often shows a single enlarged parathyroid gland
○ Ideally a single parathyroid nodule would be identified with other glands not visible
○ Occasionally, more than one gland is enlarged
Scintigraphy can be used to identify affected parathyroid gland but this is often unrewarding
Selective venous sampling for serum PTH is equally unreliable
Incidence of renal damage and failure in Primary hyperparathyroidism in dogs
Many Keeshonds and other breeds who develop PHPT do not experience renal damage
However, those who do can be very severely affected
Renal insufficiency can be recognized both before and after treatment
Treatment options for Primary hyperparathyroidism in dogs
Surgery:
- Parathyroid nodules are usually dark red in colour and can be palpated if not seen easily, attached to thyroid issue
Percutaneous ethanol injection
Heat ablation
All have high success rates
Problems associated with treatment of Primary hyperparathyroidism in dogs
Post-treatment monitoring is essential in dogs with PHPT
Ideally patients would stay in hospital for at least 5 days
The higher the pre-treatment calcium, the more likely there are to be side-effects
Severely hypercalcaemic dogs need to be pre-treated with vitamin D and calcium supplements 12-24 hours before treatment to avoid dramatic changes in calcium as PTH drops.
Clinical signs can be seen in dogs whose calcium is still relatively high, but that is substantially lower than previously
Emergency treatment for hypercalcaemia
Saline diuresis
Frusemide
Bisphosphonates (clodronate, alendronate, pamidronate)
Calcitonin
This route is rarely necessary for dogs with PHPT as the primary cause of the hypercalcaemia is generally addressed relatively quickly
Treatment of post-operative hypocalcaemia
Intravenous 10% calcium gluconate is given as a short term and emergency treatment
Needs to be given slowly over 10-30 minutes to effect – monitor ECG for bradycardia, VPCs etc.
CRI can be used until oral therapy is effective
Vitamin D analogues such as 1,25,dihydroxycholecalciferol (calcitriol) or One-Alfa (alfacalcidol) can be used
Calcium carbonate has the highest percentage of calcium and lowest cost
For long term support, commercial pet food should have enough dietary calcium to avoid the need for supplementation
Common causes of hypocalcaemia
Hypoalbuminaemia
Acute or chronic renal failure
Acute pacreatitis
Eclampsia
Hyperthyroidism
Urinary tract obstruction
Individual variation
Less common causes of hypocalcaemia
Hypoparathyroidism
Toxic causes - ethylene glycol
Iatrogenic causes
Critical illness of various aetiologies
PTH related causes of hypocalcaemia
PTH low
Calcium low
Phosphate high
Vitamin D related causes of hypocalcaemia
PTH high
Calcium low
Phosphate low
Causes of significant hypocalcaemia
Primary hypoparathyroidism (PTH low, calcium low, phosphate high)
GI malabsorptive disease (PTH high, calcium low, phosphate low)
Eclampsia (calcium low, PTH and vit D attempting to compensate but variable according to mechanism of development)
PTH low, calcium low
Hypoparathyroidism
Low calcium, high PTH
Ethylene glycol toxicity
Sepsis
Critical care patient
Phosphate enema
Eclampsia
PTH slightly high and calcium slightly low
Hypovitaminosis D
PTH high and calcium slightly low
Renal secondary hyperparathyroidism
High calcium, high PTH
Hyperparathyroidism
High calcium, low PTH
Idiopathic hypercalcaemia
Clinical signs associated with hypocalcaemia
NM excitability
- muscle fasciculations
- face rubbing
- biting/licking paws or body
- hypersensitivity to external stimuli
- stilted gait
- ataxia
Behavioural changes
- agitation
- anxiety
- vocalisation
- aggression
Other
- panting
- hyperthermia
- cataracts
When do dogs become hypocalcaemic?
Primary hypoparathyroidism
Secondary to surgery to treat primary hyperparathyroidism
When they have intestinal malabsorption syndromes such as lymphangiectasia
Sepsis
Post-partum hypocalcaemia (puerperal tetany, eclampsia)
Most common in small breeds, least common in giant breeds
Treatment for hypocalcaemia
Calcium
- IV or oral
- Can cause thrombophlebitis and skin necrosis and sloughing if SQ
Vitamin D preparations
- Differ in the time to onset of effect and what, if any modifications they require
Magnesium
Like calcium and is active in the ionised form
The second most abundant intracellular cation after calcium
A cofactor of the Na/K ATPase pump that keeps Na and K in their extra and intracellular compartments respectively
Essential for release of PTH; a deficiency can lead to functional hypoparathyroidism
