Exam 4 - Calcium Disorders Flashcards

1
Q

T/f: >99% of the body’s calcium is in bone with most of the remainder being intracellular, & <0.1% extracellular

A

true

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2
Q

what biochemical influences impact calcium homeostasis in the body?

A

PTH

calcitonin

vitamin d

cortisol

aldosterone

thyroxine

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3
Q

what action does PTH have on calcium? how does it work?

A

goal is to raise serum calcium levels

osteoclast activation & promotes calcium reabsorption in the loop of henle & distal convoluted tubules of the kidneys

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4
Q

what action does vitamin d have on calcium? how does it work?

A

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

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5
Q

what action does calcitonin have on calcium? how does it work?

A

goal is to lower serum calcium

inhibits osteoclasts & inhibits calcium reabsorption in the loop of henle & distal convoluted tubules

limited biologic effect

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6
Q

99% of calcium in bone - _______

A

hydroxyapatite

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7
Q

how is calcium released from bone?

A

osteoclasts release stored calcium (they are part of the macrophage family) & are activated by PTH when serum calcium levels are too low

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8
Q

gi calcium uptake is dependent on what?

A

vitamin d dependent!!!

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9
Q

T/F: calcium is present in gi secretions, so net loss can occur

A

true

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10
Q

how does the kidney act in the body for calcium homeostasis?

A

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

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11
Q

how does PTH & calcitonin affect the kidneys in regards to calcium homeostasis?

A

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

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12
Q

what is the basic action of PTH release in the body? where does it act?

A

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)

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13
Q

what is the basic action of vitamin d3 release in the body? where does it act?

A

increases serum calcium levels & phosphate levels

gut - stimulates absorption of calcium & phosphate from gi tract

bone - promotes PTH’s activity in bone

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14
Q

what is the basic action of calcitonin release in the body? where does it act?

A

inhibits bone resorption & decreases serum calcium levels

bone

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15
Q

why is PTH an important part of causing release of vitamin d3?

A

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)

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16
Q

where does PTH act at in the body?

A

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

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17
Q

what are some synonymous terms for vitamin d3?

A

cholecalciferol

calcitriol

1,25 hydroxycholecalciferol

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18
Q

what are the stimuli for release of vitamin d3?

A

low ECF Ca - increases pth which causes vitamin d3 activation

low ECF P stimulates vitamin d formation

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19
Q

T/F: PTH raises Ca & lowers P while vitamin d raises both Ca & P

A

true

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20
Q

where does the body get PTH?

A

parathyroid gland chief cells

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21
Q

where does the body get vitamin d?

A

either ingested or converted by uv light

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22
Q

where does the body get calcitonin?

A

thyroid gland - parafollicular c cells

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23
Q

what is the effect of PTH on serum PO4?

A

decreases serum PO4

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24
Q

what fraction of calcium is biologically active in the body?

A

free ionized calcium

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25
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
26
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
27
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
28
what are the 3 fractions of calcium as measured in serum or plasma?
1. ionized - metabolically active portion, makes up 50%, this is what defines true hypercalcemia/hypocalcemia 2. protein bound - mostly bound to albumin, influenced by acid-base status, 40%, markedly impacted by albumin status!! 3. complexed to other ions, less than 10%
29
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
30
what are the 3 general mechanisms of hypercalcemia?
1. excessive vitamin d activity/something like vitamin d - raises iCa & P 2. excessive PTH activity/something like PTH - raises iCa but lowers P 3. excessive direct osteolytic activity (something chewing at bone) - modest increases in both iCa or P
31
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
32
what are the 3 general categories of how animals present with hypercalcemia?
1. come in sick from their underlying disease - febrile from fungal disease or lame from osteosarcoma 2. come in with signs reflecting increased calcium - for dogs most often pu/pd, cats most often vague ADR/dysuria from urolithiasis 3. stumble across hypercalcemia during a wellness visit - owner is unaware of any issues, make sure it's not spurious
33
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
34
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
35
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
36
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
37
what clinical signs related to severe hypercalcemia are commonly seen?
tCa > 15 mg/dl, same as mild/moderate plus... decreased neuromuscular activity cardiac arrhythmias
38
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
39
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
40
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
41
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
42
what is the most common mechanism driving hypercalcemia of malignancy?
release by the tumor of a fetal protein that works like PTH called PTHrP
43
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
44
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
45
how is hypercalcemia of malignancy treated?
deal with the tumor & general management of hypercalcemia
46
what dogs & cats are predisposed to primary hyperparathyroidism?
dogs > 4 years old - keeshounds & elkhounds cats > 8 years old - siamese over reported
47
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
48
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
49
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
50
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
51
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
52
T/F: chronic kidney disease results in a secondary appropriate hyperparathyroidism which is needed to maintain a normal iCa
true
53
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
54
how can a switch to a low phosphate kidney diet exacerbate signs of tertiary hyperparathyroidism?
reduces gi chelation of calcium & increases uptake
55
how is tertiary hyperparathyroidism diagnosed?
advanced renal compromise is evident & PTH concentrations are elevated
56
how is tertiary hyperparathyroidism treated?
use drugs to sensitize the parathyroid glands & inhibit PTH release calcimimetics (cinacalcet) - limited use in vet med & very expensive
57
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)
58
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
59
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
60
how is vitamin d toxicity causing hypercalcemia treated?
non-specific, supportive care glucocorticoids may be helpful
61
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
62
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!
63
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
64
how does calcitonin help for emergent management of a hypercalcemic patient?
rarely used but potent way to reduce calcium - iv formulations are very expensive
65
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
66
how does furosemide help for emergent management of a hypercalcemic patient?
CRI is better than intermittent dosing - promotes calciuresis
67
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
68
what is idiopathic hypercalcemia?
feline disorder not recognized in dogs with an unclear etiology but likely something related to diet (linked to acidifying diets)
69
what is the most common cause of hypercalcemia in cats?
idiopathic hypercalcemia - usually mild, tCa < 13 mg/dl, rarely above this level
70
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
71
how is idiopathic hypercalcemia diagnosed in cats?
diagnosis of exclusion - need to rule out tumor, drugs, primary hyperparathyroidism, etc
72
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
73
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)
74
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)
75
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
76
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
77
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
78
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
79
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
80
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
81
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
82
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
83
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
84
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
85
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
86
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
87
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
88
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
89
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
90
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
91
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
92
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
93
T/F: transient hypocalcemia can occur with various conditions, but clinically important hypocalcemia is a relatively uncommon finding in small animal practice
true
94
what are the 3 mechanisms that are the general causes of hypocalcemia in small animal patients?
1. 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) 2. inadequate parathyroid - spontaneous likely immune mediated or iatrogenic following gland removal 3. overwhelming acute demand for calcium - nursing females (ecclampsia)
95
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
96
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)
97
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
98
how is primary hypoparathyroidism diagnosed?
measure PTH concentrations - will be below normal or in the lower end of the reference range
99
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
100
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
101
how is hypocalcemia from dietary imbalance diagnosed?
evaluate the diet & check vitamin d (25 OH is the form measured on routine assays)
102
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
103
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
104
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
105
why should you use caution with calcium chloride as a treatment for hypocalcemic patients?
very caustic if extravasated!!!