Calcium disorders Flashcards
What facilitates calcium being taken out of the gut? What does this mean?
- calcitriol
- dogs, cats & people need vitamin d for calcium absorption
Where does vitamin d come from for most species?
- diet rather than sunlight
What has to happen to the liver for it to not convert vitamin d?
- it has to be almost non-existent
Where can problems occur in the formation of active vitamin d (calcitriol)?
- in the kidneys
- need to have enough renal tubules available for this
What hormone is anti-calcitriol? What does this work in response to?
- FGF23: prevents calcitriol being made
- in response to high phosphate concentrations
What is the calcium level in the blood ultimately controlled by?
- Parathyroid hormone
- PTH increases calcium levels if low
- PTH control/monitors ionised calcium in the blood
EDTA contamination impact on calcium
- makes it low
- EDTA holds onto calcium in a blood sample to stop the blood from clotting
– Calcium is a coag factor in most of the coag cascade
How does albumin affect calcium?
- albumin/protein bound calcium
- hypoalbuminaemia = low protein bound calcium
– As long as ionised calcium is fine the animal with be physiologically fine i.e. not worried re specific calcium problem
What conditions/things can affect lab reading of calcium?
- lipaemia
- icterus
- haemolysis
Calcium in the circulation - different components
- ~50% ionised calcium
- ~45% bound calcium
- ~5% complexed calcium
How does phosphorus affect calcium?
- with renal dz there is more phosphate in the blood
– holds onto calcium
– therefore, increased complexed calcium fracture
– draws calcium out of the ionised calcium pool
– so total calcium can look high but ionised calcium is lower - the body can recognise this and try to get the ionised calcium back to normal
– if it succeeds can get an even higher total but normal or low ionised calcium
Renal secondary hyperparathyroidism
- FGF-23, decreased calcitriol and reduced calcium absorption → ↑PTH
- Hyperphosphatemia → increased complexed fraction of calcium
- serum total calcium normal or high
- ionised calcium low or low-normal
- high serum parathyroid hormone
What can go wrong to cause hypercalcaemia?
Increased PTH activity
▪ Primary hyperparathyroidism
Activity of PTH-like substances
▪ Humoral hypercalcaemia of malignancy
– Parathyroid hormone related peptide (PTHrP)
Increased Vitamin D activity
▪ Dietary/toxin
▪ Granulomas
Osteolysis
▪ Local destruction of bone (neoplasia)
Other/unclear mechanism
▪ Hypoadrenocorticism
▪ Feline idiopathic hypercalcaemia
▪ Raisin toxicity
Causes of total hypercalcaemia in dogs (decreasing in prevalence)
- Malignancy
- Hypoadrenocorticism
- Primary hyperparathyroidism
- Chronic renal failure
- Vitamin D toxicosis
- Granulomatous diseases
Causes of total hypercalcaemia in cats (decreasing in prevalence)
- Idiopathic hypercalcaemia
- Renal failure (total mainly, occ iCa)
- Malignancy (lymphoma and squamous cell carcinoma)
- Primary hyperparathyroidism
HARD IONS/ HOGS IN YARD
▪H - Hyperparathyroidism
▪A - Addison’s
▪R – Renal (total Ca, horses)
▪D - Vitamin D
▪I - Idiopathic
▪O - Osteolysis
▪N - Neoplasia
▪S - Spurious
▪ H - HYPERPARATHYROIDISM
▪ O - OSTEOLYSIS
▪ G – GRANULOMATOUS DISEASE
▪ S – SPURIOUS (ALBUMIN?)
▪ I - IDOPATHIC
▪ N - NEOPLASIA
▪Y - YOUNG
▪ A – ADDISON’S DISEASE
▪ R – RENAL DISEASE (total Ca, horses)
▪ D – VITAMIN D TOXICITY
Principal differentials for hypercalcaemia
Parathyroid dependent (Primary hyperparathyroidism):
- Parathyroid adenoma
- Parathyroid adenocarcinoma
- Parathyroid hyperplasia
- Calcium sensor defect (FHH; theoretical)
Parathyroid independent:
- Humoral hypercalcaemia of malignancy
- Vitamin D excess
- Granulomatous disease
- Osteolysis
- Feline idiopathic hypercalcaemia
- Hypoadrenocorticism
Further differentials for hypercalcaemia - PTH independent
Malignancy:
- Lymphoma (T-cell)
- Anal sac apocrine gland adenocarcinoma
- Other carcinoma
- Myeloma
- Osteosarcoma
- Bone metastases
- Histiocytic neoplasia
Vitamin D excess:
- Over-supplementation
- Incorrect dietary formulation
- Rodenticide
- Vitamin D analogue (Dovobet/Dovonex)
- Plants
- Granulomatous disease
- Immunological (e.g. polyarthritis)
Hyperadrenocorticism causing hypercalcaemia
▪Usually mild hypercalcaemia but other signs are used to diagnose the disease
▪Present in ~30% of Addisonian dogs
▪Usually only affects total calcium; ionized calcium is normal (?)
▪Exact mechanism unknown
▪Dehydration and increased protein concentration
▪Decreased renal calcium excretion
Idiopathic hypercalcaemia (signalment, degree of hypercalcaemia, aetiology)
▪Young to middle-aged cats
▪Mild to moderate hypercalcaemia
▪No obvious etiology
–Hypercalcaemia (total and ionized)
–Normal phosphorus concentration
–Intact PTH normal or decreased
–PTHrp undetectable
–Normal vitamin D3 concentration
–?Association with acidifying diets
Presenting signs of hypercalcaemia
- Polyuria/polydipsia
- dehydration
- Vomiting
- Anorexia
- Muscle weakness
- (consequences of urinary calculi)
- (rubber jaw/ osteopenia)
- (lymphadenopathy)
Investigation - history
Diet
▪ Supplements
▪ Unusual or unfamiliar brand
▪ Access to grapes/raisins
Access to vitamin D
▪ Supplements
▪ Rodenticide (cholecalciferol; not EU)
▪ Psoriasis medication (Dovonex/Dovobet)
▪ Certain plants
Investigation - signalment
▪ Primary hyperparathyoidism is middle-age to geriatric disease
▪ Breed predisposition (Keeshond)
Issues when both phosphorus + calcium are high in hypercalcaemia (renal secondary hyperparathyroidism)
- calcium + phosphorus complex/precipitate leading to mineralisation in the tissues that damages organs + stops function (kidney, GI mucosa)
Clinical review - LN
▪ Palpation/Imaging
Clinical review - masses other than anal sac masses - what could they be?
▪ Neoplasia
▪ Granulomas
Clinical review - anal sac masses
▪ Rectal examination may be required
▪ Sublumbar lymph nodes on imaging
Parathyroid imaging
- US
Clinical review - angiostrongylus
▪ Imaging, faecal examination
▪ Haematomas, bleeding
Clin path
▪ Ionised Calcium**
▪ Albumin
▪ Phosphorus
▪ Chloride
– Cl:P >150 (in mmol/L) high specificity for 10 HPTH and AGASAC, low sensitivity
▪ Urea and creatinine
▪ Na:K ratio (+/- ACTH stimulation)
PTH/PTHrP excess findings: total calcium, ionised calcium and phosphorus
Total calcium: increased
Ionised calcium: increased
Phosphorus: decreased or normal
Vitamin D dependent findings: total calcium, ionised calcium and phosphorus
Total calcium: increased
Ionised calcium: increased
Phosphorus: increased
Renal secondary hyperparathyroidism findings: total calcium, ionised calcium and phosphorus
Total calcium: increased
Ionised calcium: decreased or normal
Phosphorus: normal (early) increased (late)
Azoteamic hypercalcaemia - which came first?
▪Renal dysfunction → elevated total calcium: ionised calcium normal or decreased
▪Elevated calcium → renal dysfunction: ionised calcium increased
PTH dependent hypercalcaemia
- PTH increased
- Calcium increased
PTH independent hypercalcaemia
- PTH decreased
- Calcium increased
Further Investigations beyond PTH and iCa
Most common requirement is:
▪Characterise parathyroid independent hypercalcaemia
▪Low PTH and high iCa
▪No initial clinical appearance of neoplasia/granuloma
Relevant lab tests:
▪Parathyroid related peptide (PTHrP) ▪25 hydroxy-vitamin D (calcidiol)
▪1, 25 dihydroxy-vitamin D (calcitriol)
PTHrP
▪present in many humoral hypercalcemia of malignancy cases ▪Special shipping - very labile
▪Positive result helpful
25 hydroxy vitamin D
▪ 25 hydroxylation occurs in liver
▪ Excellent indicator of dietary sufficiency and excess
▪ Use for suspected cholecalciferol intoxication
▪ Rule out dietary mis-formulation
▪ Will not detect analogues
▪ Recognition of intestinal, cardiac and neoplastic risk
▪ UV adequacy
1, 25 dihydroxy vitamin D
▪ 1 α hydroxylation occurs in renal tubules
▪ 1 α hydroxylation occurs in macrophages/granulomata
▪ Lower when reduced renal tubular mass
▪ Implicated in pathogenesis of renal 20hyperPTH
▪ Will not detect analogues: Calcipotriene etc
▪ May be helpful in hypocalcaemia investigation
Generic treatment for hypercalcaemia
▪Determine urgency by Ca x P
▪ Fluids/diuresis
–5ml/kg/hr NaCl
–Furosemide 2mg/kg BID-TID – only once hydrated
– Care – check impact on potassium
▪ Glucocorticoids
– Pred 1mg/kg or equivalent
▪ Bisphosphanates
– Alendronate, clodronante, etidronate (oral)
– Pamidronate, zolendronate (IV)
Caution: impact on future diagnostics if normalise iCa or e.g. impact lymphoma with glucocorticoid
More specific treatment
Depends on cause, treat directly:
▪Neoplasia (surgery/chemotherapy)
▪Toxicities – remove and generic Tx
▪Addison’s (DOCP, Florinef)
▪Idiopathic (diet, generic therapy (bisphosphonates, glucocorticoids))
▪Primary hyperparathyroidism (surgery, percutaneous ablation)
▪Granulomatous (surgery/antimicrobials/antifungals)
▪Immune-mediated - immunosuppression
Parathyroid adenoma - peri- & post-surgical consideration
- Hyperactive nodule → hypercalcaemia
- Hypercalcaemia→ negative feedback→atrophy of normal tissue
- Remove nodule → HYPOcalcaemia
- ?”hungrybones”
- Monitor calcium post-surgically
- Support with IV calcium (any point in oral?)
- Vitamin D therapy (Calcitriol, Alfacalcidiol)
- Aim for subclinical hypocalcaemia–provide stimulus for remaining tissue to regain function
Causes of hypocalcaemia
Parathyroid dependent
▪ Primary hypoparathyroidism
– spontaneous immune mediated
– functional hypomagnesaemic
– post-surgical e.g. feline hyperthyroidism
Demand exceeds supply or mobilization
▪ periparturient tetany (eclampsia)
▪ nutritional deficiency of calcium or vitamin D
– e.g. all meat diets, severe GI disease
▪ pancreatitis with fat necrosis
[PTH and Calcitriol resistance syndromes]
Hypoparathyroidism/hypocalcaemia clinical presentation
Signs associated with neuromuscular excitability:
- muscle fasciculaton/tremors
- face rubbing
- biting & licking paws/body
- hypersensitivity to external stimuli
- stiff, stilted gait
- ataxia
- tetanic seizures
- resp arrest
- weakness
Behavioural changes:
- agitation
- anxiety
- vocalisation
- aggression
Other:
- panting
- hyperthermia
- cataracts
- lengthening or ST segment & QT interval on ECG
- 3rd eyelid prolapse in cats
Hypocalcaemia diagnosis
▪ History
▪Routine lab results, e.g., phosphorus
▪Rarely PTH, iCa and Mg measurements
Hypocalcaemia - Short term/acute therapy
▪IV calcium
– Gluconate, e.g. 0.5-1.5ml/kg over 20-30 minutes
– Borogluconate
– Chloride
▪Monitor for bradycardia
Hypocalcaemia - Long-term therapy
Aim for subclinical or low-normal hypocalcaemia
▪ Post –thyroidectomy: want to stimulate remaining tissue
▪ Primary hypoparathyroidism: reduce risk of iatrogenic Vit D toxicosis
Oral calcium supplement only if diet insufficient
▪ Sometimes used in early therapy
Vitamin D to promote Calcium uptake ▪Initially short acting (lower risk, higher cost) - Calcitriol
▪Wean to intermediate/longer acting (higher risk lower cost) - Alfacidol, dihydrotachysterol
Primary hyperparathyroidism (CS, what is it, tx)
▪ Clinical signs of hypercalcaemia
▪ Excess (inappropriately high) PTH with hypercalcaemia
▪ Therapy by surgical removal (temporary medical by bisphosphonates)
Secondary hyperparathyroidism (types, CS, tx)
Renal
▪ Signs relating to renal disease, ?rubber jaw in extreme
▪Plasma phosphate, iCa, ?FGF-23
▪ Tx phosphate restriction, ?calcitriol
Nutritional
▪ Pathological fractures
▪ Correct nutritional deficiency (avoid all-meat diets)
