Are primary bone tumors often associated with hypercalcemia in dogs or
cats?
No.
In which bones do carcinoma metastasize in cats and dogs?
Humerus, femur and vertebrae.
What are the hypothesized two primary mechanism of the pathogenesis of enhanced bone resorption (causing hyperCa)?
1) Secretion
of cytokines or factors that stimulate local bone
resorption and 2) indirect stimulation of bone resorption
by tumor-induced cytokine secretion from local immune
or bone cells. Cytokines or factors that may be secreted
by tumor cells and stimulate local bone resorption include
PTHrP, TGF-a and TGF-ß, and prostaglandins (especially
prostaglandin E2).
What is the main neoplasm which causes primary hyperparathyroidism in dogs?
Primary hyperparathyroidism
was caused by a solitary parathyroid gland adenoma
in approximately 90% of dogs, whereas
parathyroid gland carcinoma and parathyroid gland
hyperplasia each accounted for 5% of cases in one large
series.
How is primary hyperparathyroidism diagnosed?
The diagnosis of primary hyperparathyroidism
is easy in dogs and cats that have increased
serum tCa concentration, normal renal function, and
increased concentration of immunoreactive PTH. The
appropriateness of the PTH concentration must be
interpreted in relation to the serum iCa concentration.
Additional support for the diagnosis of primary hyperparathyroidism
is provided by the finding of increased
serum iCa concentration, increased serum ALP, low
serum phosphorus concentration, increased or normal
calcitriol concentration, undetectable PTHrP, and calcium-
containing uroliths. The most consistent laboratory
abnormality in dogs with primary hyperparathyroidism is
increased serum calcium concentration.
In which metabolite is vitamin D transformed to when metabolized?
25-hydroxyvitamin (calcidiol)
D –> this is what is toxic
How can hypercalcemia result from granulomatous inflammation?
Hypercalcemia can result from calcitriol synthesis by
activated macrophages during granulomatous inflammation
What is the
most common cause of ionized hypercalcemia in cats in
the United States?
Idiopathic hyperCa
What are some mechanisms causing hyperCa in IHC?
Increased bone resorption,
increased intestinal absorption, or decreased renal
excretion of calcium or combinations of these
mechanisms could be responsible for hypercalcemia.
What change in diet can decrease serum iCa and how?
The beneficial
effect of a higher fiber diet may be because of
decreased intestinal absorption of dietary calcium. The
effects of fiber on intestinal absorption are complex and
depend on the types and amounts of fiber in the diet
and other nutrients present.
Renal diet (low in calcium and phosphorus and are considered
alkalinizing)
What medication can help decrease iCa in cats that did not respond to diet change?
Pred (can last months to years)
List some treatments for hyperCa
- Treat primary cause
- IVF
- Furosemide
- Calcitonin
- GC
- Biphosphonate
- Sodium bicarbonate
- Mithramycin (severe toxicity)
- Ethylenediamine tetra-acetic acid
- Dialysis
Future considerations - Calcium channel blockers
- Somatostatin congeners
- Calcium receptor agonists
- Nonhypercalcemic calcitriol analogues
How does acidosis magnify the effects of hyperCa?
Acidosis can magnify the effects of hypercalcemia
at all serum calcium concentrations by shifting more calcium
to the ionized fraction.
What could be a consequence of alkalinity in the presence of hyperCa when administering sodium bicarb?
Too much alkalinity
can promote tissue mineralization during the presence
of hypercalcemia, so this treatment is given to effect for
only a very short while.
What is the MOA of use of steroids to decrease iCa?
Steroids exert their effects
mainly by reducing bone resorption, decreasing intestinal
calcium absorption, and increasing renal calcium
excretion
In case of which type of HyperCa, GC use can help decrease serum iCa?
Lymphoma, apocrine gland adenocarcinoma
of the anal sac, multiple myeloma, thymoma, hypoadrenocorticism,
hypervitaminosis D, hypervitaminosis A,
or granulomatous disease, some cats with IHC.
How calcitonin decreases iCa?
Calcitonin rapidly decreases the
magnitude of hypercalcemia primarily by reducing the
activity and formation of osteoclasts.
What toxicity can Mithramycin cause?
Including thrombocytopenia,
hepatic necrosis, renal necrosis, and hypocalcemia
When should EDTA be used in case of hyper iCa?
This treatment
is considered a rescue method designed to allow
other modalities time to take effect. Use of EDTA should
be reserved for crisis situations because EDTA is nephrotoxic
at higher dosages.
Clinical sx hypoCa
Common:
None
Muscle tremors or fasciculations
Facial rubbing (paresthesia?)
Muscle cramping
Stiff gait
Behavioral change
Restlessness or excitation
Aggression
Hypersensitivity to stimuli
Disorientation
Occasional:
Panting
Pyrexia
Lethargy
Anorexia
Prolapse of the third eyelid (cats)
Posterior lenticular cataracts
Tachycardia or electrocardiographic alterations
(prolonged QT–interval)
Uncommon:
Polyuria or polydipsia
Hypotension
Respiratory arrest or death
DDX for hypoCa
Common:
- Hypoalbuminemia
- Renal Failure
- Puerperal tetany (eclampsia)
- Acute renal failure
- Acute pancreatitis
- Undefined cause (mild hypocalcemia)
Occasional:
- Soft tissue trauma or rhabdomyolysis
- Hypoparathyroidism
- Ethylene glycol intoxication
- Phosphate enema
- After NaHCO3 administration
Uncommon:
Uncommon
- Laboratory error
- Improper sample anticoagulant (EDTA)
- Infarction of parathyroid gland adenoma
-Rapid intravenous infusion of phosphates
-Acute calcium-free intravenous infusion (dilutional)
- Intestinal malabsorption or severe starvation
- Hypovitaminosis D
- Blood transfusion (citrated anticoagulant)
- Hypomagnesemia
- Nutritional secondary
- hyperparathyroidism
- Tumor lysis syndrome
-Hypoadrenocorticism
What is the MOA of hypoCa in septic patients?
Hypocalcemia in sepsis, particularly during a cytokine storm, is a multifactorial process driven by pro-inflammatory mediators such as TNF-(\alpha ), IL-1(\beta ), and IL-6. The mechanism of action involves a combination of acquired endocrine dysfunction, altered calcium distribution, and increased cellular demand.
Hypocalcemia in sepsis is multifactorial, driven primarily by an acute, sepsis-induced dysfunction of the parathyroid-vitamin D axis, causing decreased parathyroid hormone (PTH) secretion, resistance to PTH at the cellular level, and impaired Vitamin D conversion. This results in reduced calcium mobilization from bone and increased loss
MOA of hypoCa in acute pancreatitis
Acute pancreatitis may be associated with hypocalcemia.
In 46 cats with acute pancreatitis,iCa concentrationwas low
in 61% of cats. Suggested mechanisms that may account
for low iCa in acute pancreatitis include sequestration of calcium
into peripancreatic fat (saponification), increased free
fatty acids, increased calcitonin secondary to hyperglucagonemia,
and PTH resistance or deficit resulting from
the effects of hypomagnesemia.
HypoCa MOA in case of small intestinal diseases?
Mechanisms for hypocalcemia could include calcium/fatty
acid complexes in the intestinal lumen that could
decrease intestinal calcium absorption. Hypovitaminosis
D from malabsorption or hypomagnesemia may have
contributed to hypocalcemia but was not evaluated.
