Calcium disorders Flashcards
How is calcium normally controlled?
- Ca lives mostly in the bones 99%
- Small amount in tissues and plasma
- Intake from diet
- Lose it from the gut
- Modulate in the kidneys
- Vitamin D has role with uptake in gut
- measure hydroxycalciferol to measure how much vitamin D is taken in diet
- active form is calcitriol (activation takes place in kidney)
- PTH acts on bones (slow and fast phase to mobilise Ca in the bones), on kidneys (promotes reabsorption) and on gut (indirect through activation of vitamin D)
What are the forms of calcium? Why is it important?
3 forms
- ionised (free) form - biologically active
- bound to albumin
- complexed calcium - bound to phosphorus
Can measure Ca, albumin and phosphate to get full picture of Ca concentration (total calcium)
What is renal secondary hyperparathyroidism? What can you see on biochem?
- FGF-23 (produced by bone), decreased calcitriol and reduced calcium absorption → ↑PTH
- Hyperphosphatemia → increased complexed fraction of calcium
- serum total calcium normal or high
- ionised calcium low or low-normal
- high serum parathyroid hormone
FGF-23 there to decrease phosphorus concentration
Triggers production of PTH
What Ca concentration marks the risk for tissue mineralisation?
5.6 mmol/l
What are most common causes of hypercalcaemia in dogs and cat?
Dogs
- Malignancy
* Hypoadrenocorticism
* Primary hyperparathyroidism
* Chronic renal failure
* Vitamin D toxicosis
* Granulomatous diseases
Cats
* Idiopathic hypercalcaemia
* Renal failure (total mainly, occ iCa)
* Malignancy (lymphoma and squamous cell carcinoma)
* Primary hyperparathyroidism
What are the main parathyroid dependent and independent differentials for hypercalcaemia?
PTH dependent
- parathyroid adenoma
- parathyroid adenocarcinoma
- parathyroid hyperplasia
- calcium sensor defect
PTH independent
- humoral hypercalcaemia of malignancy
- vitamin D excess
- granulomatous disease
- osteolysis
- feline idiopathic hypercalcaemia (links to diet)
- hypoadrenocorticism
What mechanism is associated to hypercalcaemia in hypoadrenocorticism?
- Usually mild hypercalcaemia but other signs are used to diagnose the disease
- Present in ~30% of Addisonian dogs
- Usually only affects total calcium; ionized calcium is normal (?)
- Exact mechanism unknown
- Dehydration and increased protein concentration
- Decreased renal calcium excretion
What are the clinical signs associated with hypercalcaemia?
- PUPD
- vomiting
- anorexia
- muscle weakness
How do we investigate hypercalcaemia?
Review history
* Diet
* Supplements
* Access to grapes/raisins
* Access to Vitamin D
* Supplements
* Rodenticide (cholecalciferol; not EU)
* Psoriasis medication
* Certain plants
Review signalment
* Primary hyperparathyoidism is middle-age to geriatric disease
* Breed predisposition (Keeshond)
Clinical review
* Lymph nodes
* Palpation/Imaging
* Anal sac masses
* Rectal examination may be required
* Sublumbar lymph nodes on imaging
* Other masses
* Neoplasia
* Granulomas
* Parathyroid imaging (ultrasound)
* Angiostrongylus
* Imaging, faecal examination
* Haematomas, bleeding
Clinical pathology review
* Ionised Calcium
* Albumin
* Phosphorus
* Chloride
* Cl:P >150 (in mmol/L) high specificity for 1⁰ HPTH and AGASACA, low sensitivity
* Urea and creatinine
* Na:K ratio (+/- ACTH stimulation)
* for addisons
Concurrent PTH and iCa
Beyond this
* Parathyroid related peptide (PTHrP)
* 25 hydroxy-vitamin D (calcidiol)
* Excellent indicator of dietary sufficiency and excess
- Use for suspected cholecalciferol intoxication
* 1, 25 dihydroxy-vitamin D (calcitriol)
* Lower when reduced renal tubular mass
- Implicated in pathogenesis of renal 2⁰hyperPTH
How do you interpret serum parathyroid and iCa test result?
How can we treat hypercalcaemia?
- Determine urgency by Ca x P
- Fluids/diuresis
- 5ml/kg/hr NaCl
- Furosemide 2mg/kg BID-TID – only once hydrated
- Care – check impact on potassium
- Glucocorticoids - able to promote diuresis and secretion of Ca
- Prednisolone 1mg/kg or equivalent
- impact on future diagnostics inf normalise iCa (lymphoma)
- Bisphosphanates - block osteoclasts (cells present in bone and eat bone to release Ca)
- Alendronate, clodronante, etidronate (oral)
- Pamidronate, zolendronate (IV)
Treat cause
How do you treat parathyroid adenomas?
- Peri-, Post-surgical considerations
- Hyperactive nodule → hypercalcaemia
- Hypercalcaemia → negative feedback→ atrophy of normal tissue
- Remove nodule → hypocalcaemia
- Monitor calcium post surgically
- Support with IV calcium (any point in oral?)
- Vitamin D therapy (Calcitriol, Alfacalcidiol)
- Aim for subclinical hypocalcaemia – provide stimulus for remaining tissue to regain function
What are cuases of hypocalcaemia?
- Parathyroid dependent
- Primary hypoparathyroidism
- spontaneous immune mediated
- functional hypomagnesaemic
- post-surgical e.g., feline hyperthyroidism
- Primary hypoparathyroidism
- Demand exceeds supply or mobilization
- periparturient tetany (eclampsia)
- nutritional deficiency of calcium or vitamin D e.g., all meat diets, severe GI disease
- pancreatitis with fat necrosis
- [PTH and Calcitriol resistance syndromes]
What clinical signs are associated with hypocalcaemia?
Neuromuscular excitability
- muscle fasciculation or tremors
- face rubbing
- biting and licking at paws of body
- hypersensitivity to external stimuli
Behavioural changes
- agitation
- anxiety
- vocalisation
Other
- panting
- hyperthermia
- cataracts
How would we diagnose and treat hypocalcaemia?
Diagnosis
- History
- Routine lab results, e.g., phosphorus
- Rarely PTH, iCa and Mg measurements
Short term/acute therapy
* IV calcium
* Gluconate e.g. 0.5-1.5ml/kg over 20-30 minutes
* Borogluconate
* Chloride
* Monitor for bradycardia
Long term therapy
* Aim for subclinical or low-normal hypocalcaemia
* Post–thyroidectomy: want to stimulate remaining tissue
* Primary hypoparathyroidism: reduce risk of iatrogenic Vit D toxicosis
* Oral calcium supplement only if diet insufficient
* Sometimes used in early therapy
* Vitamin D to promote Calcium uptake
* Initially short acting (lower risk, higher cost) - Calcitriol
* Wean to intermediate/longer acting (higher risk lower cost) - Alfacidol, dihydrotachysterol
