Hyprecalcaemia and hypocalcaemia disorders Flashcards
How is calcium controlled?
- PTH
- metabolites of vitamin d
- calcitonin
How does PTH increase Ca?
- KIDNEY:
- BONE
- GIT
- increases urine phosphate excretion (phosphaturia)
Actions of calcitriol
Papp
Why is calcium important?
Nn conduction and Neuromuscular transmission
- muscle contraction
- intracellular messenger involved in any number of cell signalling pathways
- coagulation
- vital maintenance of cell membrane integrity
- second messenger roles
Why is calcium important
- nn conduction and NM transmission
- mm contraction
- intracellular messenger involved in any number of cell signalling pathways
- coagulation
- intracellular Ca maintained at v low levels: vital for maintenance of cell membrane integrity, second messenger roles
How is Ca distributed in the body?
- 2 main pools: bone and ECF
- almost all calcium in bone is present as calcium hydroxyapatite (very poorly exchangeable)
- EC calcium is biologically measurable form, includes: Ca bound to albumin, Ca chelated to various compounds, Ca free in solution or ‘ionised calcium’
Describe Ca uptake in GIT
active
How is Ca stored in bones?
Ca mobilised by osteoclasts with Ca and phosphate being released
Is calcium phosphate soluble or insoluble?
insoluble (calcium and phosphate are excreted separately by kidneys)
Control of Ca
- PTH
- metabolites of vitamin D (1,25 dihydroxycholecalfierol most active)
- calcitonin
Outline PTH action
- INCRASES CA at KIDNEY: increases Ca resorpton, promoting conversion of 25 D3 to 1.25 D3
- INCREASES CA at bones: activation of osteoclast activity
- INCREASES Ca at GIT: enhanced Ca resorption from gut, mainly mediated through 1,25 D3
- INCREASES urinary phosphate excretion
Actions - calcitriol
- increases serum Ca through number of mechanisms:
- increasing GIT absorption of calcium
- facilitating renal absorption of calcium
- by mobilising Ca and PO4 ffrom bone
- calcitriol has negative ffedback on its own secretion, inhibits PTH secretion
- maintains aspects of immune system
What do PTH, metabolites of vit D and calcitonin respond to?
ionised Ca levels
Total serum Ca level = ?
2.45-2.83 mmol/L
Describe different calcium states
- ULTRAFILTERABLE CALCIUM: ionised and complexed forms
- Protein bound calcium (1/3, almost exclusively to albumin)
How to measure serum Ca
- prinicipally interested in ionised calcium
- so always also look at albumin levles
What artefacts are ionised calcium measurements prone to?
- any increase in pH increases protein binding and decreases ionised calcium
- increases in pH can occur through exposure to air, agitation, variation in [heparin]
- numerous devices can measure this ‘at bedside’
T/F: as CaPO4 is insoluble, for the mobilisation of Ca from bone to result in an increase in ionised Ca, the PO4 has to be readily removed
True
Outline disturbances in Ca balance
- needs to be significant disruption of hormonal control of Ca or the organs involved in absorption/storage/excretion of Ca
- results in hyper/hypocalcaemia
- or may result in altered bone metabolism without changes to serum calcium
Which 2 hormones are principally involved in controlling clinically signifciant alterations in serum ca concentrations?
- PTH
- 1,25 D3 calcitriol
Why do you need to look at the phosphate levels when looking into possible Ca disturbances?
it is the calcium phosphate product that is producing irreversible soft tissue calcification (
When can hypercalcaemia be ignored?
never - repeatable hypercalcaemia should always be investigated, even in absence of obviou CS
Result of prolonged untreated hypercalcaemia
(especially with normal or increased phosphate) an lead to irreversible damage to many organs especially kidneys.
CS - hypercalcaemia
- PD and PU
- weakness, lethargy, depression
- inappetence, vomiting, diarrhoea, constipation
- facial pruritus and oral discomfort
- mm twitching and fasiculations
- cardiac tachydysrhythmias
- sudden death
- or no detectable CS at all!
Clinical pathology - hypercalcaemia
- hypercalcaemia
+/- disruption to serum phosphate concentration - with or without evidence of disruption to renal function
Effect of hypercalcaemia on renal function
- hypercalcaemia interferes with tubular function so the animal has trouble concentrating its urine –> USG azotaemia
- structural renal disease if accompanied by elevated serum phosphate (CaPO4 product of >5-6)
Clinical pathology - hypercalcaemia
- hypercalcaemia
- with or without disruption to serum phosphate concentration
- with or without evidence of disruption to renal function characterised by azotaemia and IDU (inappropriately dilute urine)
- impaired renal function can result in alterations to calcium and phosphate metabolsim (hyperphosphataemia and non-ionised hypercalcaemia)
Causes - hypercalcaemia
- non-pathological reasons (rapidly growing young dogs, lab error)
- transient or interpretive (haemoconcentration, hyperalbuminaemia)
- pathological (d/t increased PTH or PTH-like activity, unrelated to increased PTH activity)
Outline pathological causes of hypercalcaemia
- INCREASED PTH ACTIVITY: primary hyperparathyroidism
- INCREASED PTH-LIKE ACTIVITY: humoral hypercalcaemia of malignancy, lymphosarcoma, anal sac adenocarcinomas, multiple myelomas etc etc
- UNRELATED INCREASED PTH or PTH1a: non-parathyroid hormone dependent causes of hypercalcaemia
Outline increased PTH and PTH-like activity
- ionised hypercalcaemia and low or non-elevated phosphate are typically present
- serum PTH likely to be ‘inappropriately not suppressed’ or there may be an elevation in serum PTHrP or some other PTH-like compound
- PTHrP is measurable, others are not:
Causes of hypercalcaemia not related to PTH-ish activity
- vitamin D toxicity (excessive supplementation, rodenticides, psoriasis creams)
- granulomatous inflammation
- hypoadrenocorticism
- CKD (grape intoxications)
- idiopathic (cats)
- significant osteolysis
Describe primary hyperparathyroidism
- keeshund markedly over-represented in developing primary hyperparathyroidism (autosomal dominat, with age-related penetrance)
- increased and autonomous PTH production by a functional neoplasm (usually solitary adenoma)
- disease of older dogs, generally over six years, uncommon in cats
- calcium negative feedback is lost
CS - primary hyperparathyroidism
- these dogs often well (hypercalcaemia may be incidental)
- often unremarkable PE
- may develop urolithiasis and then show LUT signs - dysuria, pollakiuria, haematuria
- uncommon for other signs of hypercalcaemia
Outline hypercalcaemia of chronic renal disease
- most animals with azotaemic CKD will have serum calcium in the reference range
- 14% of dogs and 38% cats are hypercalcaemic and it will be an ionised hypercalcaemia in 10% dogs, 28% cats
- hyperphosphataemia will also be present
- NOT secondary to renal hyperparathyroidism (all these patients have NORMAL Ca)
Outline idiopathic hypercalcaemia
- perhaps commonest cause of hypercalcaemia in cats
- as idiopathic, is a diagnosis of exclusion
- generally middle-aged cats
- commonly develop Ca oxalate uroliths throughout urinary tract
- monitor Ca, USG, renal function
- management: try dietary and then other management
Outline management of hypercalcaemia
- correct underlying cause or causes
- consider tx to reduce the degree of hypercalcaemia: fluid therapy, furosemide, bisphosphonates (pamidronate or alendronate)
Outline management of hypocalcaemia
- not uncommon as clinically insignificant result of hypoalbuminaemia
- BUT ionised hypocalcaemia is most frequently (dogs 3-%, cats 50%) associated CRF and:
- pancreatitis
- primary hypoparathyroidism
- iatrogenic hypoparathyroidism
- eclampsia
CS - hypocalcaemia
- abnormal neuro, neuromuscular and GIT function or combinations of all these:
- panting, anxiety and behavioural changes
- weakness with a stiff and stilted gait
- inappetance through to vomiting
- hyperthermia
- mm tremors and cramps, mm pains
Management - hypocalcaemia
- once you have determined the hypocalcaemia is clinically significant and have corrected a potential underlying cause then:
- acute IV 10% calcium gluconate
- subacutely oral medication
What does hypercalcaemia in cats seem to be caused by?
- CKD
- ‘idiopathic’ hypercalcaemia
- rest
What doses hypercalcaemia in dogs seem to be caused by?
- neoplasia
- primary hyperparathyroidism
- the rest
Management - hypocalcaemia
- frequently an unimportant problem clinically as it can result of other abnormalities
- must be tx when cause of CS it absolutely needs managing it as life-threatening
- consequently whenever detected it should ALWAYS be investigated to level that makes you comfortable
