Exam 4 - Calcium Disorders Flashcards
T/f: >99% of the body’s calcium is in bone with most of the remainder being intracellular, & <0.1% extracellular
true
what biochemical influences impact calcium homeostasis in the body?
PTH
calcitonin
vitamin d
cortisol
aldosterone
thyroxine
what action does PTH have on calcium? how does it work?
goal is to raise serum calcium levels
osteoclast activation & promotes calcium reabsorption in the loop of henle & distal convoluted tubules of the kidneys
what action does vitamin d have on calcium? how does it work?
it is essential for gi uptake of calcium - cholecalciferol has little biological activity & requires sequential hydroxylations
effect on osteoclasts is dose dependent - physiologic doses are inhibitory & toxic levels activate osteoclasts
what action does calcitonin have on calcium? how does it work?
goal is to lower serum calcium
inhibits osteoclasts & inhibits calcium reabsorption in the loop of henle & distal convoluted tubules
limited biologic effect
99% of calcium in bone - _______
hydroxyapatite
how is calcium released from bone?
osteoclasts release stored calcium (they are part of the macrophage family) & are activated by PTH when serum calcium levels are too low
gi calcium uptake is dependent on what?
vitamin d dependent!!!
T/F: calcium is present in gi secretions, so net loss can occur
true
how does the kidney act in the body for calcium homeostasis?
fine tunes calcium levels through balancing through filtration & reuptake
99% of filtered calcium is automatically reabsorbed in the proximal tubules - essentially mimics sodium, is influenced by gfr, but less is reabsorbed if gfr is high
how does PTH & calcitonin affect the kidneys in regards to calcium homeostasis?
PTH increases uptake in the later portions of the nephrons
calcitonin decreases uptake in the later portions of the nephrons
urinary calcium loss is primarily determined by serum calcium levels
what is the basic action of PTH release in the body? where does it act?
increases serum calcium levels & decreases phosphate levels (bone resorption - calcium & p release)
kidney (increases reabsorption & decreases excretion of calcium & decreases phosphate reabsorption while increasing excretion) & bone (vitamin d3 activation)
what is the basic action of vitamin d3 release in the body? where does it act?
increases serum calcium levels & phosphate levels
gut - stimulates absorption of calcium & phosphate from gi tract
bone - promotes PTH’s activity in bone
what is the basic action of calcitonin release in the body? where does it act?
inhibits bone resorption & decreases serum calcium levels
bone
why is PTH an important part of causing release of vitamin d3?
PTH controls 1a-hydroxylase in the kidney
vitamin d3 starts by being hydroxylated in the liver (25-(OH)2 vitamin d3 - first hydroxylation
further hydroxylated in the kidney by 1a-hydroxylase! becomes 1,25-(OH)2 (active form)
where does PTH act at in the body?
bone, intestines, & kidney
bone - osteoclast activation to release calcium
intestines - increases calcium & phosphate absorbed
kidneys - release of 1a-hydroxylase which hydroxylates vitamin d3 into its active form so it can act in the intestines! increases amount of reabsorbed calcium & decreases amount of phosphate reabsorbed
what are some synonymous terms for vitamin d3?
cholecalciferol
calcitriol
1,25 hydroxycholecalciferol
what are the stimuli for release of vitamin d3?
low ECF Ca - increases pth which causes vitamin d3 activation
low ECF P stimulates vitamin d formation
T/F: PTH raises Ca & lowers P while vitamin d raises both Ca & P
true
where does the body get PTH?
parathyroid gland chief cells
where does the body get vitamin d?
either ingested or converted by uv light
where does the body get calcitonin?
thyroid gland - parafollicular c cells
what is the effect of PTH on serum PO4?
decreases serum PO4
what fraction of calcium is biologically active in the body?
free ionized calcium
what is the most important component of phosphorus regulation in the body? why is this important?
renal excretion!!!!
GFR is one of the major factors influencing PO4 concentrations
if your serum levels of Ca & P move together, what do you expect the underlying etiology to be?
problem with vitamin d or less likely calcitonin
if your serum levels of Ca & P move in opposite directions, what do you expect the underlying etiology to be?
consider a problem with PTH or PTHrP
what are the 3 fractions of calcium as measured in serum or plasma?
- ionized - metabolically active portion, makes up 50%, this is what defines true hypercalcemia/hypocalcemia
- protein bound - mostly bound to albumin, influenced by acid-base status, 40%, markedly impacted by albumin status!!
- complexed to other ions, less than 10%
if you have an elevated level of tCa, what should you do? why?
need to do an ionized calcium
tCa gives you an idea of hypercalcemia - but not perfect, so you need to confirm it is real prior to working up a patient
what are the 3 general mechanisms of hypercalcemia?
- excessive vitamin d activity/something like vitamin d - raises iCa & P
- excessive PTH activity/something like PTH - raises iCa but lowers P
- excessive direct osteolytic activity (something chewing at bone) - modest increases in both iCa or P
what is your gosh darnit list for causes of hypercalcemia?
g - granulomatous (fungal disease, tuberculosis, heterobilharzia)
o - osteolysis (osteosarcoma, osteomyelitis, myeloma)
s - spurious (lab error)
h - hyperparathyroidism
d - drugs (vitamin d, thiazide, diuretics, psoriasis creams)
a - addison’s
r - renal
n - nutritional (excess in calcium or vitamin d)
i - idiopathic (common in cats - causes urolithiasis)
t - tumors
what are the 3 general categories of how animals present with hypercalcemia?
- come in sick from their underlying disease - febrile from fungal disease or lame from osteosarcoma
- come in with signs reflecting increased calcium - for dogs most often pu/pd, cats most often vague ADR/dysuria from urolithiasis
- stumble across hypercalcemia during a wellness visit - owner is unaware of any issues, make sure it’s not spurious
why do clinical signs related to hypercalcemia depend on the rate of increase?
gradual increases are often well tolerated
sudden increase can cause more compromise & hurt the kidneys
why do clinical signs related to hypercalcemia depend on the concurrent phosphorus status?
high calcium & phosphorus can cause tissue mineralization & renal injury, especially if over 70
high calcium & low phosphorus carries a minimal risk of mineralization
what clinical signs related to mild hypercalcemia are commonly seen?
mild, tCa < 13 mg/dl - compromised ability to concentrate urine (dogs only - due to abnormal interaction of ADH with its receptors, often profound, USG < 1.008), increased risk of urolithiasis from calcium oxalate stone formation (big role in cats), & gi issues primarily in cats causing poor appetite, constipation, & vomiting
what clinical signs related to moderate hypercalcemia are commonly seen?
tCa 13-15 mg/dl, same as mild plus…
renal damage - depending on phosphorus
possible triggers - pancreatitis in dogs
personality changes - dog can become aggressive
what clinical signs related to severe hypercalcemia are commonly seen?
tCa > 15 mg/dl, same as mild/moderate plus…
decreased neuromuscular activity
cardiac arrhythmias
on physical exam of a dog with hypercalcemia, what should you pay special attention to?
anal sacs!!! check for masses, they can be < 1cm
lymph nodes - check for lymphoma
on physical exam of a cat with hypercalcemia, what should you pay special attention to?
mammary chain
toes - look for squamous cell carcinoma
oral cavity - look for squamous cell carcinoma
what is the most common cause of hypercalcemia in dogs? what are the common types of tumors involved?
hypercalcemia of malignancy/humoral hypercalcemia
any tumor can cause it, but specifics
lymphoma - by far, most likely, especially mediastinal
AGASACA - especially large breeds, females predisposed
also thymoma, myeloproliferative disease, & disseminated carcinomas
what tumors can cause hypercalcemia of malignancy in cats? is this common?
mammary carcinomas & squamous cell carcinomas
much less common in cats compared to dogs
what is the most common mechanism driving hypercalcemia of malignancy?
release by the tumor of a fetal protein that works like PTH called PTHrP
what clinical signs are seen with hypercalcemia of malignancy?
signs related to hypercalcemia
+/- signs related to underlying tumor
calcium levels can rise fast with hypercalcemia of malignancy - history reflects relatively short period of hypercalcemia
how is hypercalcemia of malignancy diagnosed?
measurement of PTHrP - helpful but not definitive - positive PTHrP very strongly suggests a tumor, but has also been positive in dogs with heterobilharzia
an undetectable PTHrP doesn’t rule out malignancy - other paraneoplastic processes may raise iCa levels
imaging to identify the underlying neoplasia - imaging, cytology, biopsy
how is hypercalcemia of malignancy treated?
deal with the tumor & general management of hypercalcemia
what dogs & cats are predisposed to primary hyperparathyroidism?
dogs > 4 years old - keeshounds & elkhounds
cats > 8 years old - siamese over reported
what is the usual underlying cause of primary hyperparathyroidism?
usually a solitary adenoma - occasionally hyperplasia of more than one gland is reported, but rarely due to an adenocarcinoma
what clinical signs are seen with primary hyperparathyroidism?
related to hypercalcemia
dogs often present after weeks or months of severe pu/pd while cats are rarely overt with pu/pd
may have issues related to urolithiasis
how is primary hyperparathyroidism diagnosed?
measure serum PTH levels - may be above the upper limit or at the upper end of the range, so you need to interpret it in light of concurrent iCa levels!!!
inappropriate in the face of hypercalcemia - tells us that the parathyroid gland is behaving badly
may be able to see an enlarged parathyroid on ultrasound
how is primary hyperparathyroidism treated?
surgical removal of the affected gland
ethanol ablation - injected via ultrasound guidance into the gland
radiothermal ablation - gland is cooked using ultrasound guidance, not offered many places
patient will need calcitriol +/- calcium until other glands wake up - taper slowly as the remaining glands regain function
if a patient has hypercalcemia associated with renal disease, what do you expect calcium levels to look like?
tCa often elevated with renal disease but iCa is normal - complexed fraction is often increased, so tCa moves up
need to check iCa before pursuing secondary hyperparathyroidism
T/F: chronic kidney disease results in a secondary appropriate hyperparathyroidism which is needed to maintain a normal iCa
true
what is tertiary hyperparathyroidism?
animals with CKD/secondary hyperparathyroidism that progress to where the parathyroid glands become autonomous & lose the ability to sense iCa levels & PTH is secreted inappropriately
high iCa & PO4 results in tissue mineralization
how can a switch to a low phosphate kidney diet exacerbate signs of tertiary hyperparathyroidism?
reduces gi chelation of calcium & increases uptake
how is tertiary hyperparathyroidism diagnosed?
advanced renal compromise is evident & PTH concentrations are elevated
how is tertiary hyperparathyroidism treated?
use drugs to sensitize the parathyroid glands & inhibit PTH release
calcimimetics (cinacalcet) - limited use in vet med & very expensive
what are some common causes of vitamin d toxicity resulting in hypercalcemia?
rodenticide ingestion
dietary imbalance/over supplementation
ingestion of vitamin d containing products (psoriasis cream)
T/F: in vitamin d toxicity causing hypercalcemia, you should expect to see a concurrent increase in serum phosphorus which is likely to quickly impair renal function
true
how is vitamin d toxicity causing hypercalcemia diagnosed?
measure vitamin d levels - routine tests only identify 25 hydroxycholecalciferol & doesn’t identify agents in psoriasis cream
how is vitamin d toxicity causing hypercalcemia treated?
non-specific, supportive care
glucocorticoids may be helpful
when should you intervene in a hypercalcemic patient for emergent management?
if tCa > 15 mg/dl
calcium is rising fast
Ca X PO4 > 70
hypercalcemia & quickly progressive azotemia
why do you need to collect all of your diagnostics for a hypercalcemic patient prior to giving glucocorticoids?
it will hide lymphoma & will let fungal disease go rampant!
how do glucocorticoids help for emergent management of a hypercalcemic patient?
will reduce gi uptake - antagonize vitamin d
will promote urinary loss of calcium
dose prednisone at 1-2 mg/kg/day
how does calcitonin help for emergent management of a hypercalcemic patient?
rarely used but potent way to reduce calcium - iv formulations are very expensive
how does pamidronate or zoledronic acid help for emergent management of a hypercalcemic patient? what are the risks?
iv bisphosphonates - inhibit & hurt osteoclasts, but risk of idiosyncratic renal injury (especially pamidronate, so use with caution if creatinine is > 2.5 mg/dl)
will move calcium down within 24 hours & lasts about 2-3 weeks
risks - can have rebound hypocalcemia & risk of idiosyncratic renal injury especially when using pamidronate
how does furosemide help for emergent management of a hypercalcemic patient?
CRI is better than intermittent dosing - promotes calciuresis
how do fluids help for emergent management of a hypercalcemic patient? how should they be administered?
assess hydration status & quickly replace deficit using 0.9% saline - sodium promotes calciuresis
when hydrated, administer iv fluids, 2-3x maintenance rate - NaCl is ideal
what is idiopathic hypercalcemia?
feline disorder not recognized in dogs with an unclear etiology but likely something related to diet (linked to acidifying diets)
what is the most common cause of hypercalcemia in cats?
idiopathic hypercalcemia - usually mild, tCa < 13 mg/dl, rarely above this level
how does idiopathic hypercalcemia cause issues in cats?
sustained, mild hypercalcemia results in excessive calciuresis (calcium in urine) which triggers calcium oxalate stone formation
stones cause substantial morbidity - dysuria, obstruction, chronic kidney disease
how is idiopathic hypercalcemia diagnosed in cats?
diagnosis of exclusion - need to rule out tumor, drugs, primary hyperparathyroidism, etc
how is diet used as treatment for idiopathic hypercalcemia in cats?
start with a diet change first especially if they are on an acidifying diet - consider renal diets, anti-oxalate diets, high fiber diets
how are glucocorticoids used as treatment for idiopathic hypercalcemia in cats? what must you do prior to prescribing this drug?
prednisolone at 5-10 mg/kg/day - will lower calcium
promotes urinary loss & decreases gi uptake
never give without establishing a diagnosis - it will hide lymphoma & let fungal disease go wild (also consider weighing risk of long term steroid use vs. benefits)
how are bisphosphonates used as treatment for idiopathic hypercalcemia in cats? what risks are involved?
drugs that inhibit osteoclasts - used in people with osteoporosis
alendronate used in cats given once weekly at 10 mg/cat - adjusted based on response - substantial risk of esophagitis, so follow with water
long term use associated with pathological fractures, must be given on an empty stomach otherwise uptake is zero
weigh risks vs benefits (human recommendations limit use to 4 years)
what should you do diagnostically if you have confirmed hypercalcemia in a dog & have concurrent low phosphorus?
low p suggests PTH-type mechanism!! malignancy, primary hyperparathyroidism, or heterobilharzia
tumor hunt - repeat exam, thoracic rads, abdominal ultrasound
rule out heterobilharzia if appropriate - fecal PCR
measure PTH concentrations/PTHrP - support or rule out primary hyperparathyroidism, look for markers of cancer
what should you do diagnostically if you have confirmed hypercalcemia in a dog & have concurrent normal phosphorus?
suggests direct osteolysis or low grade vitamin d mechanism - consider osteosarcoma or osteomyelitis
what should you do diagnostically if you have confirmed hypercalcemia in a dog & have concurrent high phosphorus & minimal azotemia?
suggests vitamin d mechanisms!!! discuss diet, supplement, etc
measure vitamin d - be aware of the test limitations
what should you do diagnostically if you have confirmed hypercalcemia in a dog & have concurrent high phosphorus & substantial azotemia?
harder to figure out :/
could be vitamin d mechanism, could be related to advanced renal disease, could indicate renal damage secondary to severe or rapidly progressive hypercalcemia from any cause
what should you do diagnostically if you have confirmed hypercalcemia in a cat & have concurrent low phosphorus?
suggests PTH-type mechanism - look for malignancy & primary hyperparathyroidism
tumor hunt - repeat exam, thoracic rads, & abdominal ultrasound
measure PTH/PTHrP - support or rule out primary hyperparathyroidism, PTHrP less sensitive in cats
what should you do diagnostically if you have confirmed hypercalcemia in a cat & have concurrent normal phosphorus?
suggests idiopathic hypercalcemia - must rule out everything before assigning this diagnosis
what should you do diagnostically if you have confirmed hypercalcemia in a cat & have concurrent high phosphorus & minimal azotemia?
suggests vitamin d mechanism - discuss diet/supplements
measure vitamin d - be aware of the test limitations
what should you do diagnostically if you have confirmed hypercalcemia in a cat & have concurrent high phosphorus & substantial azotemia?
harder to figure out
same as dog - essentially all mechanisms
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with granulomatous disease?
iCa - increased
creatinine - normal to increased
PO4 - increased
PTH - decreased
PTHrP - u
vitamin d - normal
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with osteolytic disease?
iCa - increased
creatinine - normal
PO4 - increased
PTH - decreased
PTHrP - u
vitamin d - normal
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with nutritional disease?
iCa - increased
creatinine - normal
PO4 - variable
PTH - variable
PTHrP - u
vitamin d - normal
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with primary hyperparathyroidism?
iCa - increased
creatinine - normal
PO4 - decreased
PTH - high normal to increased
PTHrP - u
vitamin d - normal
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with drug-related disease?
iCa - increased
creatinine - normal
PO4 - variable
PTH - decreased
PTHrP - u
vitamin d - normal
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with vitamin d toxicity?
iCa - increased
creatinine - increased
PO4 - increased
PTH - decreased
PTHrP - u
vitamin d - increased
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with idiopathic disease?
iCa - increased
creatinine - normal
PO4 - normal
PTH - low normal
PTHrP - u
vitamin d - normal
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with addison’s disease?
iCa - increased
creatinine - increased
PO4 - increased
PTH - normal to decreased
PTHrP - u
vitamin d - normal
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with renal failure?
iCa - variable
creatinine - increased
PO4 - increased
PTH - increased
PTHrP - u
vitamin d - normal to decreased
what do you expect of your biochemical parameters of iCa, creatinine, phosphorus, PTH, PTHrP, & vitamin d in an animal with non-osteolytic tumors?
iCa - increased
creatinine - normal to increased
PO4 - normal, increased, or decreased
PTH - decreased
PTHrP - increased or u
vitamin d - normal
T/F: transient hypocalcemia can occur with various conditions, but clinically important hypocalcemia is a relatively uncommon finding in small animal practice
true
what are the 3 mechanisms that are the general causes of hypocalcemia in small animal patients?
- inadequate intake of vitamin d or calcium - vitamin d deficiency is more likely, dietary imbalance, or chronic PLE/lymphangiectasia (low magnesium impairs PTH release & exacerbates the issue)
- inadequate parathyroid - spontaneous likely immune mediated or iatrogenic following gland removal
- overwhelming acute demand for calcium - nursing females (ecclampsia)
what neuromuscular signs of hypocalcemia are commonly seen?
fasciculations or tremors
deranged sensation - facial rubbing or biting a part of the body
hypersensitivity
tetanic seizures
respiratory arrest
what behavioral signs of hypocalcemia are commonly seen? what are some other general signs seen?
anxiety, aggression, agitation, & vocalization
panting, hyperthermia, cataracts (punctate or linear opacities)
what animals are predisposed to primary hypoparathyroidism? when should you consider it as a differential?
middle aged female dogs & male cats
consider if diet is balanced & serum phosphorus is robust or increased
how is primary hypoparathyroidism diagnosed?
measure PTH concentrations - will be below normal or in the lower end of the reference range
how is primary hypoparathyroidism treated?
emergency treatment as needed
calcitriol [1,25(OH)2-vitamin d] biologically active form of vitamin d that doesn’t need to be converted further, has a rapid onset & used long term adjusting doses as needed to keep calcium on target
calcium - can taper this away when the patient is stabilized
what are some examples of various processes that cause hypocalcemia through dietary imbalances? when do we see issues most often occur with these mechanisms?
not enough vitamin d, not enough calcium, too much phosphorus
animals fed a homemade diet
how is hypocalcemia from dietary imbalance diagnosed?
evaluate the diet & check vitamin d (25 OH is the form measured on routine assays)
what is puerperal tetany? when do we see it occur? what animals are commonly affected?
milk fever/eclampsia - occurs 1-3 weeks post partum due to loss of calcium into milk
small breed dogs with large litters are most vulnerable!!! rarely seen in cats though
how is milk fever diagnosed? how is it treated?
based on history, measurement of iCa, & response to therapy
calcium gluconate IV slowly - rarely need long term supplementation
how is emergent management of hypocalcemic patients done using calcium gluconate?
0.5-1.5 ml/kg of 10% given IV over 30 minutes with concurrent ecg monitoring!!!!
6-10 ml/kg/day CRI until patient is stabilized
why should you use caution with calcium chloride as a treatment for hypocalcemic patients?
very caustic if extravasated!!!
