Ca++ Chap 52

Question 1

Severe hypercalcemia or hypocalcemia can be lethal in dogs and cats, especially if

Hypocalcemia based on total serum calcium is often

Toxicity from hypercalcemia is greatly magnified if

No calcium-specific treatment is indicated if the ionized calcium level is normal

Hypercalcemic crisis is most likely to occur when there is toxicity from

Answer 1

rapid changes in serum calcium concentration occur.

mild and less often requires calcium-specific treatment than does hypercalcemia

serum phosphorus concentration is also increased

normal

excess vitamin D metabolites circulating in the body

Question 2

Acute treatment of moderate to severe ionized hypercalcemia involves

Severe hypercalcemia that is unlikely to resolve quickly may benefit from intermittent intravenous doses

treatment of severe and symptomatic hypocalcemia involves the administration of

Ionized hypocalcemia occurs more often than predicted when only the total serum calcium is measured, especially in the critical care setting

Answer 2

IVFT, GC, furosemide, calcitonin

bisphosphonates to decrease osteoclast function

Pamidronate is the first-choice bisphosphonate in veterinary medicine, but zoledronate is more potent and gaining popularity among small animal oncologists.

IV calcium salts followed by CRI normal serum ionized calcium levels

•

Question 3

Calcium is necessary for muscle contraction because

Answer 3

mediates acetylcholine release during neuromuscular transmission

Question 4

Calcium also stabilizes nerve cell membranes by

Answer 4

decreasing membrane permeability to sodium

Question 5

which form of Ca is regulated:

Answer 5

only the circulating ionized component of total calcium is regulated

Question 6

Three forms of circulating calcium exist in serum:

complexed:

Total calcium routinely measured on serum automated biochemical analyzers measures all three of these components.

The ionized form of calcium is the biologically active

Answer 6

ionized (free), protein bound, and complexed

calcium bound to phosphate, bicarbonate, lactate, citrate, oxalate

Question 7

Calcium regulation 3 hormones and synth.:

3 extert effects on:

PTH is secreted in response to

PTH inhibited

principal action of PTH

Answer 7

PTH - parafollicular cheif cells
vitamin D metabolites
calcitonin

most effects on GIT, kidney, and bone

hypocalcemia
low calcitriol levels (1,25(OH)2D3)

serum ionized calcium levels
calcitriol

tubular reabsorption of calcium
osteoclastic bone resorption
increased production of calcitriol

Question 8

Vitamin D
unlike humans, dogs/cats photosynthesize vitamin D inefficiently in their skin .:. depend on:

vitamin D ingestion- vitamin D is first hydroxylated in:
to:

further hydroxylated to calcitriol by:

final hydroxylation by the 1α-hydroxylase enzyme system is under tight regulation and is influenced by:

Decreased levels of_____promote calcitriol synthesis

Increased levels of ______decrease in calcitriol synthesis

Increased PTH ____synthesis calcitriol

FGF-23 ____ synthesis calcitriol

Answer 8

their diet

liver to 25(OH)D3 (calcidiol)

proximal tubular cells of the kidney

PTH
calcitriol
phosphorus
ionized calcium
fibroblast growth factor 23 (FGF-23)

phosphorus
calcitriol
calcium

phosphorus
calcitriol
calcium

increased

inhibits

Question 9

calcitriol primarily acts on:

in the intestine: >
in the bone: >
in the kidney: >
in the parathyroid gland: >

two negative feedb mech: -ve

Answer 9

intestine, bone, kidney, and parathyroid gland

enhances the absorption of calcium and phosphate

promotes bone formation and mineralization by regulation of proteins produced by osteoblasts
also necessary for normal bone resorption because of its effect on osteoclast differentiation

+ve: promote calcium and phosphorus reabsorption from the glomerular filtrate

• ve feedback: inhibit the synthesis of PTH
• ve feedback: inhibit the 1α-hydroxylase enzyme system

Question 10

Calcitonin
minor when compared with the effects of PTH and vitamin D metabolites

calcitonin is produced by:

in response to:

MoA:

Answer 10

parafollicular C cells in the thyroid gland

increased Ca+

bone to inhibit osteoclastic bone resorption activity
but also decreases renal tubular reabsorption of calcium

Question 11

Sample conditions:

Answer 11

anaerobic (aerobic CO2 lost increasing pH = Ca binds more tightly to proteins - ALBUMIN - falsely decreasing ionixed albumin)

serum

fasted

Question 12

So-called correction formulas that are used to predict ionized calcium status from total serum calcium are ____

Answer 12

inaccurate

Question 13

Differential Diagnoses for Hypercalcemia

Nonpathologic (4)

Transient or Inconsequential (3)

Pathologic or Persistent/Consequential

Parathyroid dependent (4)

Parathyroid independent

• Humoral hypercalcemia of malignancy
• Hematologic malignancies (bone marrow osteolysis, local osteolytic disease)

H hyperparathy.
R Renal
A Addisons
D vit D (Rodenticide (cholecalciferol))Antipsoriasis creams (calcipotriene or calcipotriol)
I Idiopathic
O Osteolclastic (growth OSA)
N Neoplasia
S Spurious

Idiopathic hypercalcemia (cats)
Chronic renal failure
Calcinosis cutis—during recovery, especially after DMSO
Hypervitaminosis D
Iatrogenic
Plants (calcitriol glycosides)
Rodenticide (cholecalciferol)
Antipsoriasis creams (calcipotriene or calcipotriol)
Granulomatous disease (calcitriol synthesis)
Fungal
Acute kidney injury
Osteomyelitis
Hypertrophic osteodystrophy

Calcium-containing intestinal phosphate binders
Hypervitaminosis A

Answer 13

*Differential Diagnoses for Hypercalcemia1

Postprandial
Juvenile, growing animal
Laboratory error
Lipemia

Hemoconcentration
Hyperproteinemia
Hypoadrenocorticism

Parathyroid dependent

• Primary hyperparathyroidism
• Adenoma, Adenocarcinoma, Hyperplasia
• Overdose of recombinant PTH

Parathyroid independent
Humoral hypercalcemia of malignancy
-Lymphosarcoma
-Anal sac apocrine gland adenocarcinoma
-Carcinoma (e.g., thyroid, prostate, mammary)
-Thymoma

Hematologic malignancies (bone marrow osteolysis, local osteolytic disease)

• Lymphosarcoma
• Multiple myeloma
• Leukemia
• Myeloproliferative disorders
• Bone neoplasia (primary or metastatic)

Question 14

C/S hyperCa:

Answer 14

parallel the severity PU/PD, anorexia, constipation, lethargy, and weakness

Severely affected animals may display ataxia, obtundation, muscle twitching, seizures, or coma

Question 15

PE/ECG:

3 prolonged
2 shortened

Answer 15

bradycardia
prolonged PR interval
widened QRS complex
widened T wave

shortened QT interval
shortened or absent ST segment

bradyarrhythmias may progress to complete heart block, asystole, and cardiac arrest in severely affected animals

Question 16

diagnosis of hypercalcemia is confirmed with:

Answer 16

ionized Ca++ > 6 mg/dl or 1.5 mmol/L dog

>5.7 mg/dl or 1.4 mmol/L in the cat

Question 17

ionized calcium typically parallels the increase in total serum calcium except in

Answer 17

renal failue (more of bound form - phosphate, HCO3, lactate, citrate)

Question 18

Dx work-up:

Answer 18

palpate the anal sacs (dogs) peripheral lymph nodes
fundic examination (e.g., mycoses, neoplasia)
FNA/exam any masses (e.g., mammary tumors)
imaging (parathyroid ultrasonography)
PTH measurement, PTH-related protein measurement, calcidiol measurement, calcitriol measurement, bone biopsy, and bone marrow aspiration

Question 19

most common causes dog:
cats:

hint neoplasia vs renal

Answer 19

neoplasia-assoc. (lymphoma)
renal failure
hyperparathyroidism
hypoadrenocorticism

idiopathic
renal
neoplasia

phos. low vs phos high with renal

Question 20

evaluation of phosphorus concentrations may help in guiding therapy, because a calcium-phosphorus product greater than ____ represents increased risk for soft tissue mineralization

Answer 20

60

Question 21

Tx:
0.9% sodium chloride because:

Furosemide:
dose:
not in:

Answer 21

additional sodium ions provide competition for renal tubular calcium reabsorption, resulting in enhanced calciuria
0.9% sodium chloride is calcium free, thus decreasing the calcium load on the body

enhances urinary calcium
1 to 2 mg/kg
dehydrated
(CRI) of 0.2 to 1 mg/kg/hr may occasionally be needed for several hours during a hypercalcemic crisis

Question 22

Glucocorticoids:
dose:
draw-back:

Answer 22

reduced bone resorption, intestinal calcium absorption, and increased renal calcium excretion
DexSP 0.1 to 0.22 mg/kg SC or IV q12
Prednisone 1 to 2.2 mg/kg PO, SC, or IV q12h

no definitive diagnosis glucocorticosteroids may interfere with obtaining an accurate cytologic or histopathologic diagnosis as a result of cytolytic effects on lymphoid and plasma cells (e.g., lymphosarcoma, myeloma)

Question 23

Calcitonin MoA:
comes from:
adverse effects:

Sodium bicarbonate MoA:
dose:

Peritoneal or hemodialysis using calcium-free dialysate can be considered in cases refractory to traditional therapy

Answer 23

inhib. osteoclasts
Calcitonin-salmon
4 to 6 IU/kg SC q8-12, vomiting

> pH binds more tightly to proteins? or high Na ions competes for renal tubular calcium reabsorption, resulting in enhanced calciuria

Question 24

Bisphosphonates MoA:
take ____ days to maximally inhibit bone resorption
not considered drugs of choice for acute or crisis

Pamidronate
dose:
intravenously 1.3 to 2 mg/kg in 150 ml 0.9% saline as a 2-hour to 4-hour infusion

management for idiopathic hypercalcemia in cats is almost never needed because of the insidious development of hypercalcemia

Oral alendronate starting at 1 to 3 mg/kg/wk has been used for the chronic treatment of idiopathic hypercalcemia in cats. This medication may provide more long-term control of idiopathic hypercalcemia in cats compared with other proposed treatments (author’s unpublished observations). However, it should be noted that oral alendronate is not as effective as intravenous bisphosphonate therapy in the acute setting. Oral bisphosphonates can cause esophageal irritation and have been reported to cause abdominal discomfort, nausea, and vomiting

Answer 24

decrease osteoclastic activity
1-3 days

zoledronate is more potent

repeated in 1 week
but the salutary effect may last for 1 month

Question 25

Calcimimetics belong to a new class of drugs i.e.
MoA:

Answer 25

Cinacalcet

activate the calcium sensing receptor and thus decrease PTH secretion

Cinacalcet has been marketed for use in humans to treat renal secondary hyperparathyroidism and nonsurgical primary hyperparathyroidism.

Question 26

Hypocalcemia
Decreased total serum calcium is a relatively common electrolyte disturbance in critically ill dogs and cats. In two separate previous studies, the prevalence of ionized hypocalcemia was ___ in sick dogs and ___ in cats

Answer 26

31% in sick dogs and 27% in cats

Question 27

Signs of hypocalcemia are often not seen until serum total calcium concentrations are less than __ ionized__

animals show few signs even with lower calcium levels

with rapid development of hypocalcemia MOST show clinical signs

i.e. CS

Answer 27

6.5 mg/dl
<4 mg/dl

Muscle tremors or fasciculations
Facial rubbing
Muscle cramping
Stiff gait
Behavioral change
Restlessness or excitation
Aggression
Hypersensitivity to stimuli
Disorientation
Prolapse of third eyelid (cats)

Question 28

ECG

if you remember one remember — prolonged:

Answer 28

Severely affected animals may have decreased inotropy and chronotropy
bradycardia
prolonged QT interval (because of prolonged ST segment)
wide T waves
atrioventricular block

QT

tachycardia, ECG alterations (i.e., prolonged QT interval), refractory hypotension, and respiratory arrest are all possible complications of ionized hypocalcemia

Question 29

most common cause of a total serum hypocalcemia is

Correction formulas - are they useful?

Answer 29

hypoalbuminemia

mild and typically no clinical signs result

been advocated in the past to correct calcium levels for a low albumin, but these formulas do not accurately predict ionized or total calcium concentrations and are therefore not recommended

Question 30

second most common cause of hypocalcemia

one condition that will require long-term calcium-specific treatment:

If the serum phosphorus level is above the reference range at the same time that hypocalcemia is discovered, the most likely diagnoses to rule out:

6 other ddx:

Answer 30

Renal dysfunction

Primary hypoparathyroidism

renal dysfunction,
pancreatitis
excessive phosphorous intake
primary hypoparathyroidism

1. Eclampsia
2. Primary hypoparathyroidism
   Idiopathic/Iatrogenic (postoperative bilateral thyroidectomy)
3. Phosphate enema
4. Hypomagnesemia (PTH secretion and receptor effects)
5. CaEDTA
6. Transfusion

Question 31

refractory hypoCa++ look for what e- derangment and explain MoA:

Answer 31

Hypermagnesemia and hypomagnesemia can impair the secretion of PTH, and PTH actions on its receptor, so measurement of serum magnesium (preferably ionized magnesium) is important, especially in animals with refractory hypocalcemia

Question 32

dogs with sepsis - presence of ionized hypocalcemia has been shown to be a ____

Answer 32

negative prognostic indicator JVECC 2010 fletcher study

Question 33

Tx acute
how long does it take to take effect?
NEVER give it how

Answer 33

CaGluc. 0.5- 1.5mg/kg over 20 min
30 min
SQ - necrosis and euth

Question 34

More chronic:
CRI of elemental calcium:
until oral calcium administration and or vitamin D metabolites can be used to control serum calcium concentrations

Vitamin D metabolites should also be started early if the hypocalcemia is expected to persist, because

Answer 34

1 to 3 mg/kg/hr IV

it may take several days for intestinal calcium transport to be maximized. Calcitriol is the preferred active vitamin D metabolite because it has a quick onset of action, short plasma half-life, and relatively short biologic effect half-life (important if overshoot hypercalcemia occurs).

Question 35

For long-term therapy (e.g., primary hypoparathyroidism) oral calcium

goal of therapy with hypoparathyroidism is not to return calcium levels completely to normal, why?

Goal levels to just below normal

calcium carbonate, calcium lactate, calcium chloride, calcium gluconate - and all are dosed at 25 to 50 mg/kg q24h (divided and given twice a day).

Tums - Calcium carbonate is the most common form of calcium used and is generally well tolerated. Calcitriol can also be used at the previously mentioned dosages.

Answer 35

deleterious effects (hypercalciuria despite normocalcemia in the absence of basal effects that PTH normally has on renal tubules).

PTH usually increases renal absorption

Question 36

Ionized Hypocalcemia in Critically Ill Dogs
M.K. Holowaychuk B.D. Hansen T.C. DeFrancesco S.L. Marks JAVIM 2009

Background:

Methods: Prospective observational study of sequentially enrolled dogs. Blood was collected within an hour

Results: The incidence of iHCa (iCa < 1.11 mmol/L) was 16%. The presence of iHCa was associated with longer ICU (P= .038) and hospital (P= .012) stays but not with decreased survival (P= .60). Dogs with sepsis as defined by ≥3 SIRS criteria and a positive culture were more likely to have iHCa (P= .050).

Conclusions and Clinical Relevance: finding of iHCa upon admission to the ICU predicted a longer duration of ICU and hospital stay. Septic dogs with positive cultures were more likely to have iHCa.

Answer 36

Background: Ionized hypocalcemia (iHCa) is a common electrolyte disturbance in critically ill people, especially those with sepsis. The cause of the iHCa is not entirely understood and is likely multifactorial. Critically ill people with iHCa have longer hospital stays and higher mortality rates compared to people with normocalcemia.

147 Animals
blood was collected within an hour of admission

iCa < 1.11 mmol/L was 16%
presence of iHCa was assoc w. longer ICU not with decreased survival
Dogs with sepsis as defined by ≥3 SIRS criteria and a positive culture were more likely to have iHCa (P= .050).

finding of iHCa upon admission to the ICU predicted a longer duration of ICU and hospital stay. Septic dogs with positive cultures were more likely to have iHCa.

Question 37

incidence of ionized hypocalcemia (iHCa) in critically ill human patients is substantial, occurring in as many as 88% of ICU patients

MoA unknown

Critically ill people with iHCa spend a significantly
longer time in ICU
higher case fatality rates compared with people with normocalcemia

septic people with iHCa when compared with normocalcemic septic patients increased LOH and death

Additionally, human trauma patients with iHCa have more severe injuries and more frequently suffer prehospital cardiac arrest as the degree of iHCa worsens

Answer 37

iHCa in critically ill people include surgery, pancreatitis, severe trauma, and burn injuries. iHCa also occurs commonly in septic patients with an incidence of 20–82%

including parathyroid gland dysfunction, cytokine‐mediated suppression of PTH
vitamin D deficiency
hypomagnesemia, calcium chelation

Question 38

JAVIM 2009 For every dog, pH‐corrected (to pH 7.40) ionized calcium concentrations

alkalosis =

incidence of iHCa in this study population was 16%, suggesting that iHCa is less common in critically ill dogs vs ppl

Critically ill dogs with ___,___,___ were more likely to have iHCa

Dogs diagnosed with sepsis based on ≥3 SIRS criteria and a positive culture were also significantly more likely to have iHCa.

These results suggest that ionized calcium is an important variable to measure in certain subsets of critically ill dogs

pH affects the plasma ionized calcium concentration, as alkalemia increases protein binding of calcium and reduces ionized calcium.

For this analysis, all ionized calcium values were adjusted to a pH of 7.4, using a correction formula built into the analyzer that has not been validated for dogs. Although the uncorrected ionized calcium concentration is the biologically relevant value, we used the pH‐corrected values to mitigate the confounding effect of the wide range of pH values identified in the dogs in this study.

Answer 38

Additionally, the presence of iHCa was not associated with survival, but did predict an increased duration of hospital and ICU stay

reduces ionized calcium _increases protein binding

renal failure
diabetic ketoacidosis (DKA)
pancreatitis

sepsis >3

In light of the results of studies in people, a comparatively low incidence of iHCa was detected among critically ill dogs in this study; however, this might have been due to the exclusion of previously fluid resuscitated dogs with more severe illness at presentation. Similarly, no difference in outcome was detected in this study, in contrast to the findings documented in studies evaluating iHCa in critically ill people. This could be due to the small numbers of dogs with metabolic and renal disease or sepsis included in this study, as these are the diseases, in which iHCa has been found to have an effect on survival. Future investigations should focus on these subsets of critically ill dogs, in addition to traumatized dogs, to determine whether ionized calcium can be used as a predictor of outcome. Similarly, several ionized calcium measurements during the course of hospitalization would be ideal, to determine whether changes in ionized calcium values have an impact on survival.