Lectures 2-4: Calcium Disorders in Small Animals Flashcards
Ligand gated channels in most cells are controlled by?
hormones and neurotransmitters
Voltage-gated channels in muscle and nerve cells are controlled by?
electric membrane potential
Calcium is highly regulated. By what?
ATP-dependent Ca pump, Na-Ca exchanger, organelle storage, ligand gated channels, voltage gated channels
What are the diffusible types of extracellular calcium?
Free/ionized and complexed
What is the most biologically active calcium?
free/ionized
What is complex calcium bound by?
non-protein anions like citrate, lactate, phosphate
Protein bound calcium is mostly bound to?
albumin
What is the storage site for calcium and phosphorus?
bones
What is bone resorption?
osteoclasts break down bone and releases Ca and P into bloodstream
Where are calcium and phosphorus filtered?
glomerulus
Where are calcium and phosphorus absorbed?
proximal tubule
PTH decreases the amount of phosphorus that can be reabsorbed from the tubule so it goes where?
urine
What regulates minute to minute iCal?
PTH
PTH is secreted from where?
chief cells in the parathyroid gland
PTH does what?
- increases calcium resorption in bone
- increases tubular calcium reabsorption
- increases activation of calcitriol/vit D
What stimulates PTH release?
low calcium
high phosphorus
low calcitriol
What does PTH do to calcium?
increases it
What does PTH do to phosphorus?
decreases it
What does PTH do to calcitriol?
increases it
A hypercalcemic patient should have an appropriately (high/low) PTH.
low
A hypercalcemic patient should not have a (high/normal/low) PTH.
normal or high
PTH does what more specifically to phosphorus?
promotes excretion and inhibits reabsorption
In vitamin D toxicity cases, what will your calcium and phosphorus be?
high calcium and phosphorus
What does calcitonin do?
tones down the calcium
Where is calcitonin secreted from?
parafollicular cells from thyroid gland
What is PTH-rp?
a PTH related protein that is a cause of humoral hypercalcemia of malignancy
PTH-rp is produced by what tumors:
lymphoma, AGASACA, multiple myeloma
When do you worry about metastatic mineralization of tissues?
When the Ca X Phos >60-80
What will happen to calcium and phosphorus with excessive PTH?
high calcium and low phosphorus
What will happen to calcium and phosphorus with low PTH?
low calcium and high phosphorus
What’s your first approach for hypercalcemia?
iCal to confirm
c/s of Hypercalcemia
stones: pupd, AKI, dehydration
bones: osteoporosis
abdominal moans: nausea, vomiting, constipation
psychic groans: lethargy, muscle weakness, confusion
If there is low calcium, what does it do to your neurons?
makes em super excitable
What are some renal effects of hypercalcemia?
hypercalcuria
nephrogenic DI
PUPD
calcium oxalate crystals/stones
can result in AKI
If you have a hypercalcemic patient with AKI, what are your two DDx?
neoplasia
vitamin D toxicosis
Dx Approach for Hypercalcemia
confirm with iCal
hx, pe
minimum database
PTH, PTH-rp, vit D
imaging
aspirate LN, liver, spleen, BM
What signs of hypercalcemia do you need to treat patient immediately?
dehydration
azotemia
CNS signs
weakness
Ca x Phos >60-80
ER Tx for Hypercalcemia
0.9% NaCl 2-3x maintenance
Loop diuretics
Bisphosphonates IV
Glucocorticoids if neoplasia ruled out
Bisphosphonate Side Effects
1 Osteonecrosis of jaw
#2 GI upset
#3 esophagitis
List causes for hypercalcemia in dogs.
H - hyperparathyroidism
O - osteolytic
G - granulomatous
S - spurious
I - idiopathic
N - neoplasia
Y - young animal
A - addison’s
R - renal
D - vitamin D toxicosis
What are the mechanisms of hypercalcemia?
increased PTH or PTH-rp
increased calcitriol
unknown
non-pathologic
Describe primary hyperparathyroidism.
Abnormal gland produces PTH that does not respond to high calcium feedback.
Most often caused by a solitary adenoma or hyperplasia, so glands are atrophied.
PHPTH Diagnosis
PTH inappropriately increased in the face of hypercalcemia, either high end normal or increased
Breed PHPTH Predisposition
Keeshonds
c/s of PHPTH
asymptomatic
insidious onset
pupd, weakness, anorexia, lower urinary tract signs
PHPTH Work up
PE, minimum database
iCal/PTH/PTH-rp
neck ultrasound
What will you likely see on neck ultrasound in a PHPTH patient?
one large gland or all normal
Primary Hyperparathyroidism Tx
1 parathyroidectomy
Post-Parathyroidectomy Care
monitor iCal for hypocalcemia
calcitriol +/- calcium carbonate supplement and taper over 3-4mo
PHPTH Prognosis
excellent with surgery unless malignant or patient is in renal failure
Other PHPTH Tx that we don’t usually do
ethanol or heat ablation
medical mgmt with bisphosphonates
Secondary Hyperparathyroidism have what causes?
renal and nutritional
Describe renal secondary hyperparathyroidism
driven by low calcitriol in the beginning and high phosphorus in advanced stages.
expect low Ca, low calcitriol, high phosphorus and no activation of vitamin D
Decreased GFR increases what?
phosphorus
Why do we care about renal secondary HPTH?
it is a progressive disease and can ultimately lead to renal mineralization, while it also demineralizes bone so you’ll see fibrous osteodystrophy (rubber jaw) and pathologic fractures
Nutritional Hyperparathyroidism is from?
an imbalanced diet
What values of Ca, P, and calcitriol will you see with nutritional HPTH?
low Ca
low calcitriol
high phosphorus
Describe PTH-rp
related protein that has similar action to PTH but hormone does not come from parathyroid gland, it comes from the cancer
What percent of hypercalcemic dogs have cancer?
50%
What is the most common cause for hypercalcemia in dogs?
neoplasia
What are the mechanisms for hypercalcemia with neoplasia?
humoral hypercalcemia of malignancy
osteolysis (osteosarcoma)
ectopic production of PTH
paraneoplastic syndromes (AGASACA, lymphoma, multiple myeloma)
When do you give steroids in cases of hypercalcemia?
When you have a definitive diagnosis bc we don’t want to give them in cancer cases!
Describe granulomatous hypercalcemia.
Granulomatous inflammation stimulates macrophages to produce calcitriol which leads to increased Ca and P.
can be bacterial, fungal, sterile panniculitis, etc.
What is the most common cause of hypercalcemia in cats?
idiopathic
T/F: PTH-rp of 0 rules out neoplasia.
false
Describe hypervitaminosis and hypercalcemia.
vitamin D toxicosis rapidly increases Ca and P in the gut
caused from intoxication of rodenticide or anti-psoriasis cream, excessive supplementation
c/s: acute pupd, acute renal failure, tissue mineralization, vomiting, anorexia, lethargy, seizure
Tx for Idiopathic Hypercalcemia in Cats
1: Diet change to high fiber, low Ca (novel, hydrolyzed)
#2: Prednisolone
#3 PO Bisphosphonates
Describe non-pathologic hypercalcemia.
It’s in young, growing animals. Correlates to bone growth so high tCa, high P, high ALKP enzyme. Can also be post-prandial or spurious.
Why do we see neuromuscular signs with hypocalcemia?
calcium is involved in release of ACh. with low calcium, there is an increase in nervous system excitability
c/s of Hypocalcemia
muscle tremors, facial rubbing, restlessness, anxious, aggressive, seizures, hyporexia, weight loss
What is the approach to hypocalcemia?
measure a fasted iCal
hx, pe, minimum database
PTH
vitamin D
When to do ER tx for hypocalcemia?
when hypocalcemic and clinic!
What is the ER treatment for hypocalcemia?
calcium gluconate IV slowly over 30min, monitor eck for bradycardia, shortened QT or vomiting
benzos for seizures
What is maintenance tx for hypocalcemia?
calcitriol +/- calcium carbonate (tums)
titrate to maintain iCal
Diseases that cause Hypocalcemia
P - primary hypoparathyroidism
E - eclampsia
E - ethylene glycol toxicity
A - acute pancreatitis
R - renal failure
S - severe GI disease
What are the mechanisms for hypocalcemia?
- low PTH
- low calcitriol
- increased Ca utilization
- increased Ca consumption
Describe Hypoparathyroidism.
Occurs due to destruction or atrophy of parathyroid glands - usually immune mediated in young animals.
Low PTH, low tCal, low iCal, WNL or high P
Can be primary or secondary (iatrogenic)
What breeds often get primary hypoparathyroidism?
golden retrievers, poodles, miniature schnauzers, GSDs
c/s of Hypoparathyroidism
seizure, face rubbing, biting/licking paws, etc
*can worsen with excitement, exercise or petting
How do you diagnose primary hypoparathyroidism?
iCal/PTH
How do you treat primary hypoparathyroidism?
calcitriol +/- calcium carbonate for life
What can cause secondary hypoparathyroidism?
iatrogenic - thyroid, parathyroid or other neck surgery
With secondary hypoparathyroidism, what do you expect for iCal, PTH, and P?
low PTH
low iCal
high or normal P
In the face of hypocalcemia, PTH should be?
low
Why can you see decreased gut absorption of vitamin D?
lymphangiectasia
malabsorptive disease ~ PLE
Why can excessive calcium loss occur?
eclampsia in lactating patients; it’s usually very severe and life threatening
How to treat eclampsia?
IV calcium then PO calcitriol
When is eclampsia risk in a cat?
peak lactation or 3-17d before birth
When is eclampsia risk in dogs?
1st 4wks of lactation and small breeds have a higher risk
If a dystocia comes in, what should you check?
calcium, glucose and electrolytes
Describe ethylene glycol toxicity and hypocalcemia.
metabolites of ethylene glycol chelate calcium into calcium oxylate crystals, leads to renal injury and loss of Ca into urine and eventually death
Describe the relationship between severe, acute pancreatitis and hypocalcemia.
Saponifcation of peri-pancreatic fat
Which diseases do you see c/s from hypocalcemia?
primary hypoparathyroidism
eclampsia
+/- gut malabsorption
Which diseases do you rarely see c/s from hypocalcemia?
renal disease
ethylene glycol
acute pancreatitis
