CO9 Laboratory Evaluation of Calcium, Phosphorus & Magnesium Flashcards
1
Q
Serum Calcium – 3 Fractions
A
- 50% is ionized (diffusible, able to do work within cells)
- 40% is bound to albumin (machine preferentially measures this)
- 10% is bound to non-protein anions
2
Q
Calcium – Hormonal Regulation
A
- Parathyroid hormone (PTH)
> Ca release from bone
> Ca retention by kidneys
> Renal P excretion
> Renal calcitriol formation - Activated Vitamin D (calcitriol)
> Increases intestinal Ca and PO4 absorption - Calcitonin
> Decreases Ca release from bone - PTH-rP
> Secreted by some tumours
> Fetal Ca balance
> Function in adults is unknown
3
Q
hormonal response to hypercalcemia?
Phosphorus balance?
A
– ↑ calcitonin
– ↓ PTH
– ↓ calcitriol (active vit D3)
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– P variable
4
Q
hormonal response to hypocalcemia?
Phosphorus balance?
A
– No increase in calcitonin
– ↑ PTH
– ↑ calcitriol (active vit D3)
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– P variable
5
Q
can we measure Ca relevant hormones? special requirements?
A
yes, all of them, but especially
PTH
PTH-rP
> special shipping requirements
6
Q
what calcium measurements can we prepare in clinic
A
- Serum – redtop
– Total serum Ca2+ (mmol/L) - Ionized Ca2+
– iCa
– Physiologically important component
– SPECIAL HANDLING!
7
Q
Interpret Calcium with:
A
- Albumin
- Phosphorus > get together and mineralize tissue
- Acid-Base balance > determines how much is bound to albumin (increased H+ bumps Ca2+ off albumin, and we will measure less calcium in that instance because the albumin fraction is the one that is most measured by the machine)
8
Q
Causes of Hypocalcemia
A
- Hypoalbuminemia – ionized Ca normal
- Pancreatitis > saponification of fat; Ca loves to bind to damaged tissue; precipitates out into this damaged fatty tissue
- Kidney failure > not enough tissue left to make vit D
– Hypovitaminosis D
– Dogs, cats, cattle - Hypoparathyroidism
- Decreased intake or absorption (ruminants) * Milk fever
9
Q
Clinical Signs of Hypocalcemia develop when?
A
- develop only when ionized Ca is low
10
Q
Clinical Signs of Hypocalcemia in dogs
A
- Dogs: generalized tetany, seizures
11
Q
Clinical Signs of Hypocalcemia in cows
A
- Cows: hyperesthesia and tetany early, paresis to flaccid paralysis, later
- Nervousness, anorexia, stilted gait
- Hyperventilation, numbness
12
Q
Causes of Hypercalcemia
A
- Kidney disease in horses
- Vitamin D toxicosis (eg. rat bait, psoriasis cream)
- Osteolytic bone lesions
- Primary hyperparathyroidism
- Hypoadrenocorticism > don’t have production of certain hormones, connection not well understood
- Multiple myeloma (2 reasons) > plasma cell disease, results in IG production; IGs can attract calcium to them and be measured as part of the total fraction
> also can cause lytic bone lesions - Neoplasia – PTH-rp production > T cell lymphoma, anal sac adenocarcinoma, certain carcinomas
13
Q
Clinical Signs of Hypercalcemia
A
- Relatively few clinical signs
- PU/PD
– Interferes with concentrating ability
– Tends to cause renal failure by tubuloglomerular mineralization - Lethargy, weakness, constipation
- Mineralization of soft tissue
– When calcium and phosphorus are increased
– Calcium x phosphorus product - > 5.6 predicts tissue mineralization
- > 70 in US units
14
Q
Dog with protein losing enteropathy, hypocalcemia
> what can hypocalcemia be due to?
A
- hypocalcemia can be due to low albumin levels
15
Q
5-year-old F Holstein
Hx: 3 days fresh, recumbent
- decreased Ca, P
- AST, CK increased
Whats the problem
A
- decreased Ca, P: feature of milk fever
- AST, CK increased due to down cow squishing her own muscles
16
Q
Her 7-year-old MN English Bull Terrier, “Spencer” has been lethargic for no reason
Is drinking more and peeing more
Could you please look at his CBC and biochem?
- high Ca
- high SDMA
- high ALT
Whats going on? Dx approach?
A
- SDMA has been touted as an early marker of kidney dz in animals
- ALT is leakage from liver… some liver damage going on? not super high, could be inflammation
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- main Ddx is; why is Ca so high?
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- Albumin?
- History of vitamin D ingestion?
- Mass in ventral neck region?
- Ionized calcium
- PTH/PTH-rp
- Cancer hunt…
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Sent for additional testing:
Ionized Ca - H
PTH - L
PTH-rp - H
ALT - H
> low PTH means normally functioning parathyroid
on US, diffusely enlarged liver > paraneoplastic lymphoma in this case
17
Q
Sx: 6-month-old female DSH
Hx: Acute onset of tachypnea, vomiting, weakness
CBC: Stress leukogram
Glucose - H
Urea - H
Creat - H
Ca - H
P - H
K - H
USG 1.022
whats next?
A
- glucose H probably due to stress in young cat
- Ca and P are regulated inversely, should never both be H together
> do product, if >6 tissue mineralization
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- urea, creat, USG telling us that kidney is damaged > this is the reason for high K (can’t get out of the body, backing up in blood)
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Next we do blood gas:
pH - L
pCO2 - H
pO2 - L
HCO3- - L
- resp and metabolic acidosis
> low pO2 tells us there is something about the membrane of the alveolus that is preventing oxygen from getting in and preventing CO2 from exiting the body (mineralization of tissue? like to bind to alkaline tissue like the lung)
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Dx - cat has been poisoned with rat bait > takes up to 42 hours for clinical signs to show up and by then it is too late :(
18
Q
Phosphorus Measurement
- how to?
A
- Serum – red top (whatever plain tube you use)
> ‘Inorganic phosphorus’ – mmol/L - Avoid hemolysis
– RBCs contain phosphorus
19
Q
Hypophosphatemia - is it common? when do we see it?
A
- Less common finding
– Parturient paresis in cows
– Vitamin D deficiency / malabsorption
– Diabetic ketoacidosis & treatment with insulin (phosphorus goes into cells at the same time glucose does)
– Early hyperparathyroidism and humoral hypercalcemia of malignancy (HHM) > increase in PTH or PTH-rP; causes phosphaturia (however at a certain point in the disease the Ca overrides everything and causes kidney damage, so that the phosphaturic effect is lost as the kidney damage becomes apparent)
20
Q
Hyperphosphatemia in Dogs
- when is it ok? what else will we see?
A
- in a growing dog, increased serum P in otherwise healthy dog
> increased ALP as well (induced from liver or bone) - growing individual has phosphorus being brought into bone, for bone creation
> ALP is also high from bone growth
21
Q
Hyperphosphatemia in Dogs
- in a 12 year old dog is it ok?
- also has severe azotemia, USG 1.01
A
- not ok in a dog this age
- severe azotemia = marked increase in urea and creat
> USG 1.01 is isothenuric
> kidney dz
> high serum P because it is backing up into blood due to renal damage
22
Q
connection between increased serum P and hemolytic anemia
A
- P is in RBCs, lysis releases it
23
Q
is serum Mg a good indicator of total body Mg?
A
Serum Mg poor indicator of total
body Mg
– 3 fractions similar to Ca
– Ionised Mg, but is not measured
– NB: cows can have near-normal serum Mg and tetany due to low CSF Mg
24
Q
what tube to measure Mg
A
serum - red top
25
Magnesium hormonal regulation? general regulation?
* Some hormonal influence but not strictly hormonally regulated like Ca
1. Intestinal absorption
2. Renal excretion
3. Milk excretion
26
Excretion of Mg
* Feces – unabsorbed
* Kidney
–GFR down > Mg up
–GFR up > Mg down
* Mammary gland during lactation
– Milk has 5x as much Mg as serum
27
reasons for Hypomagnesemia
1. Hypoalbuminemia (hypoproteinemia)
2. Malabsorption > GI loss
3. GFR up > renal loss increased
4. Cattle on Mg-deficient or K-rich pasture
> can end up with hypomagnesemic tetany
28
Clinical Signs Associated with Hypomagnesemia
* Neuromuscular signs
– Hyperexcitability
– Tremors, fasciculations, ataxia, tetany
– Cardiac arrhythmias – heart sounds loud
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- will not go down on its own, heart is so loud > how to differentiate from milk fever
29
Several cows in a herd of milking shorthorns Hx: Twitching ears, some staggering and falling, on new grass:
Ca - L
P - N
Mg - L
whats going on? pathogenesis and predisposing factors?
Hypomagnesemic Tetany
* Lush spring grass pastures low in Mg
* Fertilized with Ca, nitrates, ammonia, sulphates and K > decreased Mg in grass
* Low dietary Mg > ↓PTH > ↓Ca
* Occurs rapidly when moved to fresh pasture
* Neurologic signs
* Pregnancy/lactation are predisposing
30
Hypermagnesemia causes
* Decreased GFR > Mg down
– Dehydration
– Anuric kidney failure or urinary obstruction
* Iatrogenic
– Mg-containing laxatives or antacids
31
Total serum calcium mainly reflects the fraction of calcium that is:
A. Free and available to to work
B. Bound to non-protein anions
C. Bound to albumin
C. Bound to albumin
32
Which of the following are reasons for hypocalcemia? Select all that apply.
A. Hypomagnesemia
B. End-stage kidney failure
C. Hypoalbuminemia
D. Hyperalbuminemia
E. Hypoparathyroidism
F. Hypoadrenocorticism
A. Hypomagnesemia
> Yes, it has to do with the sensors on the parathyroid gland. In a sense, Mg and Ca compete for the receptors at a set ratio. If there is less Mg, then more receptors are available for even the decreased numbers of Ca to bind, so the gland is “tricked” into thinking there is adequate calcium, so it does not produce PTH
B. End-stage kidney failure
> Yes, eventually there are too few cells to create active vitamin D, so hypocalcemia ensues
C. Hypoalbuminemia
> yes, this is quite a common reason for a mild hypocalcemia
E. Hypoparathyroidism
> Yes, but it’s not common
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D. Hyperalbuminemia
> No, this is a cause of hypercalcemia
F. Hypoadrenocorticism
> No, it is associated with hypercalcemia, and the mechanism is still
unknown
33
A cat has hypercalcemia. If the cause is not hyperparathyroidism, what should PTH be?
A. Increased
B. Low-end normal
C. High-end normal
B. Low-end normal
> Yes, the reference interval for PTH is close to zero, so low PTH technically can be measured. But in the face of hypercalcemia, the parathyroid gland with normal function will produce as little PTH as possible, so we would measure low-end normal PTH.
34
An older dog has hypercalcemia with normal albumin. What is the order of causes from most to least likely?
A. Lymphoma > hyperparathyroidism > renal failure > bone growth
B. Bone growth > hyperparathyroidism > renal failure > lymphoma
C. Hyperparathyroidism > lymphoma > renal failure > bone growth
D. Renal failure > lymphoma > bone growth > hyperparathyroidism
E. Lymphoma > hyperparathyroidism > bone growth > renal failure
A. Lymphoma > hyperparathyroidism > renal failure > bone growth
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– Lymphoma (or other common neoplasms, such as apocrine gland adenocarcinoma of the anal sac) are common in older dogs and are associated with humoral hypercalcemia of malignancy
– Hyperparathyroidism is not a common neoplasm
– Renal failure in dogs and cats is more commonly associated with normocalcemia (due to renal secondary hyperparathyroidism) or hypocalcemia (in end-stage kidney disease)
* NB: renal secondary hyperparathyroisidm keeps calcium within the reference interval, it would not make it higher because that is dangerous and can lead to tissue mineralization, especially in kidney disease where phosphorus becomes increased from decreased GFR
* If calcium is increased in association with kidney disease, it is more likely from complexing with non-protein anions
– Bone growth hypercalcemia may be seen in young animals, and rarely in association with fracture healing, so it is the least likely reason for hypercalcemia in an older dog.
35
An older dog has hypercalcemia with normal albumin. What are the most appropriate next steps? Select all that apply:
A. Measure ionized calcium
B. Measure PTH / PTHrp
C. Digital rectal exam
D. Abdominal ultrasound
E. Ask the owners if there is warfarin in the house
F. Ask the owners if anyone in the house has psoriasis
A. Measure ionized calcium
– Yes, this is reasonable, because you want to “prove” it’s a true hypercalcemia
B. Measure PTH / PTHrp
– Yes, these can be ordered together with ionized Ca (probably cheaper than doing them one by one)
C. Digital rectal exam
– Absolutely! Apocrine gland adenocarcinoma of the anal sac is common in older dogs
D. Abdominal ultrasound
– Absolutely! Lymphoma is common in older dogs and may affect the spleen, liver, GI tract, etc.
E. Ask the owners if there is warfarin in the house
– Warfarin is not associated with hypercalcemia (vitamin D-type rodenticides are associated with hypercalcemia)
F. Ask the owners if anyone in the house has psoriasis
– Possibly, some of the creams for psoriasis are vitamin D analogues...
36
Why might a horse in end-stage kidney disease have normal calcium while a dog or cat might have hypocalcemia? Select all that apply.
A. Horses don’t have 1-alpha-hydroxylase
B. Horses eat a lot of calcium in the diet
C. Cats and dogs have 1-alpha-hydroxylase
A. Horses don’t have 1-alpha-hydroxylase
– Yes, so even if they have diminished kidney tissue, it won’t affect calcium status
B. Horses eat a lot of calcium in the diet
– Yes, calcium in horses comes in because there is so much of it in the diet
C. Cats and dogs have 1-alpha-hydroxylase
– Yes, and if they have diminished kidney tissue, there is decreased generation of activated vitamin D
37
I am concerned a patient has humoral hypercalcemia of malignancy and I want to run PTH-rp and ionized Ca. What is my next step?
A. Call the laboratory – there are special shipping requirements for these tests
B. Send in an EDTA tube
C. Send in spun down serum
A. Call the laboratory – there are special shipping requirements for these tests
– YES!! Call the lab, sending in the wrong sample type or sending the correct sample type in the wrong way (e.g., not on ice) will result in a test that can’t be run, will require the patient to come back in, will result in a delay in therapy.
38
A cow has neuro signs and a normal magnesium on the serum biochemical profile. Does this mean that it’s impossible for her neurological to be caused by low CSF magnesium?
A. Yes
B. No
C. Insufficient data
B. No
– Correct. magnesium in blood does not track linearly with CSF magnesium, so her neuro signs could be caused by low CSF magnesium
