endocrinology (hypercalcemia in cats) Flashcards
what are the key role of calcium in normal physiological processes
calcium is important in:
- neuromuscular transmission
- enzyme activity
- blood coagulation
- muscle contraction (including skeletal, smooth and cardiac muscles)
- calcium mediates vascular smooth muscle contraction and maintains blood vessel tone and hence blood pressure
- calcium is the most abundant component of the skeleton
list the three organ systems responsible for calcium homeostasis
gastrointestinal tract
kidneys
bones
what are the hormones involved in calcium regulation
parathyroid hormone
calcitriol
calcitonin
what are the PTH roles
PTH increases calcium reabsorption in the distal convoluted tubules of the kidney
PTH decreases phosphate reabsorption from the proximal tubules
PTH stimulates osteoclastic bone resorption and increases the number of osteoclasts on the bone surface to release calcium and phosphate from bone
what are the calcitriol’s roles
calcitriol is the active form of vitamin D
it increases the absorption of calcium and phosphate from the GI tract and also reabsorption in the renal tubules
what are the calcitonin’s roles
calcitonin is a potent calcium lowering hormone
it acts predominantly on bone to inhibit osteoclastic bone resorption
describe briefly the process of calcium regulation
PTH is produced from chief cells in the parathyroid gland in response to ionised hypocalcemia
calcitriol is activated in the kidneys under the influence of the enzyme 1-alpha-hydroxylase
- cats have low levels of vitamin D in their skin
- unlike in humans, it is not synthetised in the skin in response to sunlight
- therefore, cats are dependent on dietary intake and vitamin D is often supplemented in pet foods
calcitonin is secreted from C cells in the thyroid gland in response to hypercalcemia
describe the physiological response to hypercalcemia
the normal physiological response to hypercalcemia includes:
- decreased production of PTH from the parathyroid gland
- increased production of calcitonin from C cells in the thyroid gland
- decreased production of calcitriol in the kidneys due to direct inhibition and also decreased PTH production
this results in:
- reduced release of calcium and phosphate from bone due to reduced PTH concentrations
- increased renal excretion of calcium, due to decreased PTH and calcitriol concentrations
- decreased intestinal absorption of calcium due to decreased calcitriol concentration
what is the risk with hypercalcemia
identification of hypercalcemia and implementation of appropriate therapy is important as soft tissue calcification is likely to occur if the calcium*phosphate product becomes increased (>5.6 mmol²/l²)
mineralisation of renal tissue may result in nephron injury causing a decline in renal function and azotemia
hypercalcemia may promote formation of calcium oxalate uroliths
hypercalcemia may play a role in pancreatitis
describe all the forms of calcium in the body
approximately 99% of total body calcium is stored in bones in the form of hydroxyapatite crystals
extracellular calcium exists in three forms:
- ionised calcium: around 50%, it is the biologically active form
- complexed calcium: around 10%, it is complexed with anions such as phosphate, lactate or bicarbonate - protein-bound calcium: around 40%, it is bound to proteins mainly albumin
describe pre-analytical factors that can contribute to a low ionised calcium
results for ionised calcium are lower in heparinised blood samples compared with serum samples
kittens will have increased concentrations due to increased bone turnover until 12 months of age
exposure to air will lead to loss of CO2 and an increase in pH, this promotes calcium binding to protein and results in a decreased ionised calcium concentration
in acidemic patients, hydrogen ions will displace protein-bound calcium ions and increase the ionised calcium concentration
a cat with ionised calcium concentration > 1.40 mmol/l is generally considered to be hypercalcemic
what are the clinical signs accompanying hypercalcemia
they are often vague and non-specific
lethargy and weakness may result from depressed excitability of muscular and nervous tissue
anorexia, vomiting and constipation may be a consequence of decreased contractility of the smooth muscle in the GI tract
muscle twitching and potentially seizures may be seen due to direct effects of hypercalcemia on the central nervous system
cardiac arrhytmias can also develop due to direct effects on cardiac tissue
PU/PD is less frequent than in dogs may be due to the higher capacity of cats to concentrate urine
what are the main differentials for hypercalcemia
spurious results:
- non-fasted sampling
- hyperlipidemia
- hyperproteinemia
- hemoconcentration
- laboratory error
- physiological growth in young animals
hypercalcemia in cats is mostly idiopathic, with CKD and neoplasia also being common causes
hypoadrenocorticism and primary hyperparathyroidism are very rare in cats
what would be your diagnostic approach for hypercalcemia
biochemistry
- ionised calcium should be measured to confirm hypercalcemia if total calcium is elevated
- hypercalcemia should be demonstrated to be persistent
- a cat with an ionised calcium concentration > 1.40 mmol/l is generally considered to be hypercalcemic
- full biochemical analysis should be undertaken including renal function and phosphate concentration
parathyroid hormone
- it allows to assess if hypercalcemia is parathyroid dependent or parathyroid independent
- the majority of cats will have parathyroid-independent hypercalcemia
- if the PTH concentration is in the upper two-third of the reference interval or is increased, it suggests a parathyroid-dependent cause
parathyroid hormone related peptide
- PTH-rp can be measured if malignancy is suspected
- normal value does not fully exclude neoplasia
vitamin D metabolites
- calcitriol and calcidiol can be measures
- calcitriol reflects metabolically active vitamin D
- calcidiol reflects cholecalciferol or ergocalciferol ingestion following hydroxylation
what findings in urinalysis could be suggestive of hypercalcemia
presence of calcium oxalate crystals or uroliths could suggest hypercalcemia (or ethylene glycol toxicity)
why is diagnostic imaging useful
thoracic and abdominal imaging can be helpful in screening for neoplasia or granulomatous lesions
soft tissue calcification can occur when calcium*phosphate product is > 5.6 mmol²/l²
the kidneys and gastric mucosa are the predominant organs to be affected and this may be visualised on X-ray or CT images
X-ray may also identify calcium oxalate nephroliths, ureteroliths or cystoliths
what treatment could be implemented in patients with a severe acute rise in calcium concentration
promoting diuresis
- IV fluid therapy and furosemide (1-2 mg/kg q 8-12h) administration
- isotonic saline is the fluid of choice as it does not contain calcium
- furosemide acts to inhibit calcium reabsorption in the loop of Henle
- thiazide diuretics should not be used as these enhance the reabsorption of calcium in the renal distal tubules
can glucocorticoids be used to treat hypercalcemia
glucocorticoids reduce bone resorption, decrease intestinal absorption and increase renal excretion of calcium
avoid steroids if the underlying etiology remains unclear
prednisolone 0.5-1 mg/kg q 12-24 h
dexamethasone 0.1-0.2 mg/kg/24h
how bisphosphonates can be helful in treating hypercalcemia
bisphophonates exert their activity by reducing the number and activity of osteoclasts
alendronate 5-20 mg/cat PO q 7 days administered after fasting to optimise GI absorption
how calcitonin can be useful in hypercalcemia
calcitonin has short-lived effects and may be associated with side effects
used in emergency if needed 4-6 UI/kg SC q 8-12h
salmon calcitonin is the most potent form available
how a dietary change could be useful for treating hypercalcemia
dietary change is one of the most important aspects of management in cats with idiopathic hypercalcemia
high fiber diets can be fed to bind intestinal calcium, thus reducing its absorption
wet diets can also be helpful in promoting diuresis and generally have a lower calcium content than dry diets
- diets formulated for management of calcium oxalate urolithiasis may be considered as these are restricted in calcium and decrease urinary acidification
diets containing < 200mg/100 kcal of calcium and with Ca:P ratio < 1.4:1 are recommended
- Chia seed (2g/cat/day) could be tried as they respect this nutritional profile
how would you manage hypercalcemia associated with CKD
in cats with early and mid-stage CKD, iCa is normal or low and total calcium is normal or increased
- this is the result of increased phosphate concentration associated with reduced renal clearance forming complexes with ionised calcium
reduce phosphate retention through feeding a renal diet that is restricted in protein and phosphate
intestinal phosphate binders without calcium salt can be used
it is important to note that some cats can develop hypercalcemia when being fed a renal diet
- increased phosphate intake may lead to resolution of hypercalcemia
how would you manage hypercalcemia associated with hyperparathyroidism
if primary hyperparathyroidism is confirmed, the abnormal parathyroid tissue should be surgically resected with close monitoring for development of hypocalcemia or recurrent laryngeal nerve damage
in nutritional hyperparathyroidism it is low calcium or an altered calcium:phosphate ratio in the diet that stimulates productionn of PTH
- it is not generally associated with hypercalcemia
- it may be recognised more commonly with the increasing popularity of feeding bone and raw food diets. It is the same with all-meat diets
- nutritional secondary hyperparathyroidism is typically associated with a predominantly meat diet, as they are low in calcium but high in phosphate which stimulates PTH production
explain malignacy associated hypercalcemia
less common in cats than in dogs
hypercalcemia ca develop through humoral mechanisms or through osteolytic mechanisms
primary bone neoplasia is rarely associated with hypercalcemia
squamous cell carcinoma and lymphoma are the two most common neoplasms associated with hypercalcemia
both total and ionised calcium are increased and therefore, PTH concentration should be low
explain hypercalcemia associated with hypervitaminosis D
there is typically a parallel increase in calcium and phosphate concentration
PTH concentration will be low
the presence of soft tissue calcifications may be more suggestive of vitamin D toxicity as both calcium and phosphate rise in parallel, resulting in an increased calcium*phosphate product
explain hypercalcemia associated with granulomatous disease
uncommon cause of hypercalcemia
hypercalcemia can result from granulomatous inflammation because macrophages can synthesize calcitriol without negative feedback regulation
calcitriol can be high and calcium normal
hypercalcemia has been associated with mycobacteria, FIP, toxoplasmosis, nocardiosis, cryptococcosis and actinomyces rhinitis
explain the link between hyperthyroidism and hyperparathyroidism
60-80% of cats with hyperthyroidism have concurrent hyperparathyroidism
total and iCa concentrations tend to be either normal or slightly decreased
hyperphosphatemia is more frequently observed
- these findings are most likely due to the effects of thyroid hormone on bone turnover and renal excretion
hypocalcemia and/or hyperphosphatemia will cause compensatory increase in PTH secretion
