Calcium Homeostasis in Small Animals Flashcards
What hormone do the parathyroid glands secrete and what is its function?
Parathyroid Hormone (PTH) - PTH raises calcium levels by releasing calcium from your bones, increasing the amount of calcium absorbed from your small intestine and increasing resorption of Ca from the kidneys
Note: in the bone and intestine, both Ca and P is increased
But in the kidneys Ca is increased and Phosphate is excreted
What are the tests available to us which can allow us to assess Calcium homeostasis?
- Total calcium: includes ionized, protein-bound and complex
- Ionized Calcium alone
- Phosphate: Ca and P are closely intertwined
- PTH
- PTHrp (rp = related protein): usually low concentrations in adults, and is produced by certain neoplasms
- Vitamin D
What is the preferred measurement of Calcium in assessing Ca homeostasis?
- Ionized Calcium: the metabolically active form
Where is PTH excreted?
Via the kidneys, thus dependent on healthy kidney function to ensure accumulation does not occur
A high PTH level can suggest over-production or inadequate renal function leading to the accumulation of PTH
Interpretation of PTH levels should always be done with ________
Ionized Calcium
This is because the PTH level may be within the reference range BUT at an inappropriate level for the calcium concentration
25(OH)D is the _______ form of Vitamin D
inactive
1,25(OH)2D is the _______ form of Vitamin D
active
Hypercalcemia is associated with what clinical signs/ diseases?
GI: vomiting/ anorexia, constipation, and important risk factor in the development of pancreatitis
Neurological: listlessness/ weakness, stiff gait and shivering
Renal: PU/PD, Urolithiasis, UTI and the onset and progression of renal failure
Mild Hypercalcemia is around ____ mmol/L
Apparent Hypercalcemia is around ____ mmol/L
Life-threatening Hypercalcemia is around ____ mmol/L
Mild = 3.4 mmol/L
Apparent = 3.75 mmol/L
Life-threatening = 4.75 mmol/L
You obtain the routine blood results of a dog, and it suggests Hypercalcemia, is this a concern/ what should be done next?
May not be a concern
72-82% of hypercalcemia cases are due to Non-pathological causes: e.g. non-fasting, physiological, lab error, hyperlipidemia, spurious, hemoconcentration, hyperproteinemia, and hypothermia
18-28% os hypercalcemia cases are due to Pathological and persistent causes: Parathyroid disease, neoplasia, idiopathic, hypoadrenocorticism, kidney failure, skeletal lesions, toxins
What to do?
1) Consider non-pathological causes (described above)
2) Repeat or assess ionized Calcium
3) Assess Phosphate
4) Investigate potential complications: UTI, Urolithiasis and kidney failure
What are the important clinical differentials for Hypercalcemia?
HARD IONS
Hyperparathyroidism
Addison’s Disease
Renal disease
D: Hypervitaminosis D
Idiopathic (only occurs in cats)
Osteolytic
Neoplastic
Spurious
What are the 5 important DDx of hypercalcemia in the dog specifically?
1) Neoplasia
2) Kidney disease
3) Addison’s
4) Hyperparathyroidism
5) Hypervitaminosis D
What are the 3 important DDx of hypercalcemia in the cat specifically?
1) Neoplasia (30%)
2) Kidney disease (25%)
3) Idiopathic (15%)
What neoplasias are associated with hypercalcemia?
Humoral hypercalcemia = due to the production of a PTH-like hormone
- Lymphoma (20-40%)
- Anal sac adenocarcinoma (25-50%)
- Other carcinomas
Local osteolytic hypercalcemia = due to the destruction of bone
- Multiple myeloma (20%)
Why is hypercalcemia associated with Addison’s Disease?
Cortisol is required for the excretion of Ca in the kidneys
Will also see hyperkalemia, hyponatremia and pre-renal azotemia
Renal disease is associated with secondary and tertiary hyperparathyroidism + hypercalcemia, why?
Renal failure leads to excessive loss of calcium in the kidneys and subsequent hypocalcemia. The Parathyroid glands create excessive amounts of PTH to keep calcium in its narrow range, resulting in hyperplasia of the Parathyroid gland and thus Secondary hyperparathyroidism, which can progress to tertiary
Will also see hyperphosphatemia and renal azotemia
What is the difference between primary, secondary, and tertiary hyperparathyroidism?
Primary hyperparathyroidism (pHPT): Hypercalcemia results from abnormally active parathyroid glands.
Secondary hyperparathyroidism (sHPT): Hypocalcemia results in reactive overproduction of PTH.
Tertiary hyperparathyroidism (tHPT): Hypercalcemia results from untreated sHPT, with continuously elevated PTH levels.
What is the most common cause of primary hyperparathyroidism in dogs?
What is the breed most affected by this?
Cause: Adenoma (90% of cases)
Usually older dogs (Keeshounds are predisposed)
- Is an autosomal dominant trait
There is a suggested breed-disposition in cats for primary hyperparathyroidism, which breed is most typically seen?
Siamese cats
What are the most common clinical signs in dogs associated with primary hyperparathyroidism?
- PU/PD (50%)
- Urolithiasis or UTI (50%)
- No obvious clinical signs (40%)
- Kidney failure (3 - 30%)
- Lethargy and weakness
You suspect primary hyperparathyroidism, what additional tests can be done to confirm diagnosis?
- U/S: finding parathyroid masses (most are 4 - 10mm)
Masses under 4mm arent usually seen- too small
What are the most common causes of Hypervitaminosis D?
- Iatrogenic: accidentally give too much Vitamin D while trying to treat hypovitaminosis D
- Accidental: food, rodenticides, day blooming jessamine, calcipotrial (cream used to treat Psoriasis in humans, which dogs seem to like to eat)
- Granulomatous Diseases: Macrophages produce excess Vitamin D while fighting infections such as Blastomycosis, Aspergillosis, Angiostrongylosis or Panniculitis
Describe Idiopathic Hypercalcemia (IHC) in cats
The term IHC describes a syndrome in cats that have ionized hypercalcemia for which no underlying cause can be identified, even after extensive medical evaluation.
What are the most commonly associated clinical signs when referring to Idiopathic Hypercalcemia in cats?
- Non-symptomatic and therefore incidental finding is the most common presentation
- In symptomatic cats, clinical signs include (mild) weight loss, anorexia, vomiting, diarrhoea, constipation, lethargy, and signs of lower urinary tract disease (pollakiuria, stranguria, hematuria). Calcium oxalate stones may be present due to increased calciuresis
You are presented with a dog that has hypercalcemia, increased iCa and increased PO4, what does this suggest?
- Kidney disease
- Addison’s Disease: confirmed with ACTH stim test
- Hypervitaminosis D
You are presented with a dog or cat that has hypercalcemia, increased iCa and normal or decreased PO4, what does this suggest?
- Hyperparathyroidism
- Neoplasia
You are presented with a cat that has hypercalcemia, increased iCa and normal PO4, what does this suggest?
- Idiopathic hypercalcemia
- Hyperparathyroidism
You are presented with a dog or cat that has hypercalcemia, increased iCa and normal or decreased PO4, increased PTH, normal PTHrp, what does this suggest?
Hyperparathyroidism
You are presented with a dog or cat that has hypercalcemia, increased iCa and normal or decreased PO4, decreased PTH, high PTHrp, what does this suggest?
Neoplasia
What is the treatment of hypercalcemia?
1) IV Fluids of 0.9% saline at 2x maintenance: aiming to increase renal excretion of Ca concentrations
2) +/- Furosemide: 2 mg/kg/8 hrs IV or SC
3) +/- Pamidronate: 1.3 - 2.0 mg/kg in 140 mls of 0.9% saline over 2 hours. Provides a prolonged decrease in Calcium levels
What is Pamidronate, and how does it work?
- Used for the treatment of Hypercalcemia
- Is a bisphosphate drug
- Decrease calcium concentrations by inhibiting bone resorption
Note: also been shown to:
- Reduce tumor cell viability and proliferation
- reduce angiogenesis
- increase the efficacy of anti-neoplastic therapy
What are the side effects associated with using Pamidronate?
- Hypocalcemia
- Renal toxicity after repeated high dose IV use
- Infusion site reactions if not used IV
In an animal with hypercalcemia, what drug should be avoided?
Prednisolone
Although it can decrease calcium levels by increasing Ca excretion and interfering with Vitamin D, it doesn’t do so very effectively and it can interfere with diagnostic tests later on
You diagnose an animal with hypercalcemia and have confirmed lymphoma or another neoplasia. What drug might you use?
- L-asparaginase: 10,000 IU/M2 IV
Measure iCa every 12 hours for 72 hours
What is the treatment of choice for primary hyperparathyroidism?
Surgical removal: parathyroidectomy
note: hypocalcemia is a possible side effect after this and thus must be supplemented to stabilize the patient
You have diagnosed Idiopathic hypercalcemia in a cat, what is the treatment/ management?
1) Dietary change: increased fibre, renal diet to combat crystals in the urine
2) +/- Prednisolone if diet alone doesn’t work (5-10 mg/cat/day)
3) Alendronate (10 mg weekly): irritates esophagus when swallowing, must give coated with butter and follow up with water
What are the DDx for hypocalcemia?
- Spurious: hypoalbuminemia (but iCa will be normal)
- Marked: Hypoparathyroidism, Eclampsia and usually seen after bilateral thyroidectomy
Mod-Mild: Pancreatitis, nutritional deficiency, drugs/toxins (ethylene glycol, phosphate/EDTA/citrate/bicarbonate), Renal disease or Urethral obstruction, Intestinal malabsorption, metabolic alkalosis, SIRS
You are presented with an animal that has muscle tremors, tetany, seizures, aggression, abdominal pain, and/ or Lenticular cataract, what might this suggest?
Hypocalcemia
How can we diagnose hypocalcemia?
- measure Ca levels
- measure PTH levels to distinguish the cause if hypoparathyroidism
What is the treatment for Hypocalcemia?
Acute Tx:
1) 10% Calcium gluconate: 1 - 1.5 ml/kg slowly IV over 10-20 mins
or, 6.5 - 10 ml.kg over 24 hours
Note: 10% ONLY in small animals, as 40% can cause vascular damage
Never give SC as it can cause skin necrosis
Chronic Tx:
1) Oral Calcium + Vitamin D
